A method for synthesizing 2-aryl-4-phosphono-4H-chromene compounds

Abstract

The application discloses a synthesis method of 2-aryl-4-phosphoryl-4H-chromene compounds, which comprises the following steps: dissolving 2-hydroxychalcone, diaryl phosphine oxide and mercury triflate in an organic solvent, and reacting at 80-100 DEG C; after the reaction is completed, 2-aryl-4-phosphoryl-4H-chromene compounds are obtained through separation and purification; the synthesis method is simple, the reaction condition is mild, and the operation is convenient; the raw materials are easy to prepare; the reaction byproduct is water; and the method has the advantages of high atomic economy, green environmental protection and the like.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and more particularly to a method for synthesizing a 2-aryl-4-phosphono-4H-chromene compound. Background Technology

[0002] Tinones are a class of compounds containing benzopyran structures. Tinones and their derivatives are widely found in various plants and are important structural units in some natural products. Tinones and their derivatives possess a variety of physiological activities. For example, 4H-tinone compounds exhibit antibacterial, antiproliferative, antitumor, antiallergic, and antioxidant activities, thus 4H-tinones have been widely used in the development of pharmaceutical formulations and drug candidates. Furthermore, the importance of phosphonylated heterocyclic compounds in synthesis and medicinal chemistry has also attracted widespread attention from chemists.

[0003] 2-Aryl-4-phosphono-4H-chromene compounds possess both 4H-chromene and phosphono-acyl structural units, making them an important class of compounds with diverse physiological activities. Currently, only two methods exist for synthesizing these compounds, as shown in the following formulas:

[0004]

[0005] Currently, methods for synthesizing 4-phosphono-4H-chromene compounds are very limited and have certain limitations, such as low yields and a narrow range of applicable substrates. Therefore, there is an urgent need to find a method for synthesizing 4-phosphono-4H-chromene compounds with high yields and broad applicability. Summary of the Invention

[0006] The purpose of this invention is to provide a method for synthesizing 2-aryl-4-phosphono-4H-chromene compounds. This method synthesizes 2-aryl-4-phosphono-4H-chromene compounds through a mercuric trifluoromethanesulfonate-catalyzed Michael addition / cyclization / dehydration reaction. The reaction byproduct is water, which has the advantages of high atom economy and green environmental protection.

[0007] The technical solution adopted in this invention is:

[0008] A method for synthesizing a 2-aryl-4-phosphono-4H-chromene compound includes the following steps: dissolving 2-hydroxychalcone, diarylphosphine oxide, and mercuric trifluoromethanesulfonate in an organic solvent, reacting at 80–100 °C, and after the reaction is complete, separating and purifying to obtain the 2-aryl-4-phosphono-4H-chromene compound, the general reaction formula of which is as follows:

[0009]

[0010] Among them, R 1 Selected from hydrogen, alkoxy, C1-C 10 Alkyl, halogen, or nitro groups;

[0011] R 2 and R 3 Each is independently selected from aryl and 5-6 heteroaryl groups.

[0012] In some implementation schemes, R 1 Selected from hydrogen, methoxy, halogen, C1-C3 alkyl, or nitro; R 2 and R 3 Each is independently selected from substituted aryl, unsubstituted aryl, and 5-6 membered heteroaryl; further, the substituents of the substituted aryl are selected from hydrogen, halogen, alkoxy, and C1-C5 alkyl, and the number of heteroatoms in the 5-6 membered heteroaryl is 1, 2, or 3, and the heteroatoms are selected from one or more of N, O, and S.

[0013] Furthermore, the number of heteroatoms is 1, and the heteroatoms are selected from S.

[0014] In this invention, the order in which 2-hydroxychalcone, diarylphosphine oxide, and trifluoromethanesulfonic acid are added is not limited. They can be added sequentially in the order of 2-hydroxychalcone, diarylphosphine oxide, and trifluoromethanesulfonic acid, or in the order of trifluoromethanesulfonic acid, 2-hydroxychalcone, and diarylphosphine oxide, etc.

[0015] The molar ratio of 2-hydroxychalcone to diarylphosphine oxide is (0.1–0.5):(0.12–0.6).

[0016] In some embodiments, the molar ratio of 2-hydroxychalcone to diarylphosphine oxide is 0.3:0.36.

[0017] The molar ratio of hydroxychalcone to mercuric trifluoromethanesulfonate is (0.1–0.5):(0.01–0.05).

[0018] In some implementations, the molar ratio of hydroxychalcone to mercuric trifluoromethanesulfonate is 0.3:0.03.

[0019] In this invention, one or more of acetonitrile, toluene, dichloromethane, 1,2-dichloroethane, ethyl acetate, methyl acetate, and propyl acetate are selected, with methyl acetate being preferred.

[0020] Furthermore, the volume of the organic solvent used is 20 times the molar amount of 2-hydroxychalcone.

[0021] In this invention, silica gel column chromatography is used for separation and purification, and the eluent ratio is dichloromethane:ethyl acetate = 40:1.

[0022] In this invention, the reaction time is 20 to 48 hours, preferably 30 hours.

[0023] In this invention, the 2-aryl-4-phosphono-4H-chromene compound is selected from the following compounds:

[0024]

[0025]

[0026] Unless otherwise stated, the following terms used in this invention are intended to have the following definitions. A particular term should not be considered unclear unless specifically defined, but should be understood in its ordinary sense.

[0027] The term "C1-C6 alkoxy" refers to alkyl groups containing 1 to 6 carbon atoms that are attached to other parts of a molecule by an oxygen atom. Examples of C1-C6 alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy (including n-propoxy and isopropoxy), butoxy (including n-butoxy, isobutoxy, s-butoxy and t-butoxy), pentoxy (including n-pentoxy, isopentoxy and neopentoxy), hexoxy, etc.

[0028] The term "C1-C3 alkoxy" refers to alkyl groups containing one to three carbon atoms that are attached to other parts of a molecule by an oxygen atom. Examples of C1-C3 alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy (including n-propoxy and isopropoxy), etc.

[0029] The term "halogen" refers to fluorine, chlorine, bromine, and iodine.

[0030] The term "C1-C6 alkyl" is used to refer to a straight-chain or branched saturated hydrocarbon group consisting of 1 to 6 carbon atoms. The C1-C6 alkyl group includes C... 1-5 C 1-4 C 1-3 C 1-2 C 2-6 C 2-4 C1-C6 alkyl groups, etc.; they can be monovalent (e.g., methyl), divalent (e.g., methylene), or polyvalent (e.g., methine). Examples of C1-C6 alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (including n-propyl and isopropyl), butyl (including n-butyl, isobutyl, s-butyl, and t-butyl), pentyl (including n-pentyl, isopentyl, and neopentyl), hexyl, etc.

[0031] The term "C1-C3 alkyl" is used to refer to a straight-chain or branched saturated hydrocarbon group consisting of 1 to 3 carbon atoms. The C1-C3 alkyl group includes C1-C2 and C2-C3 alkyl groups, etc.; it can be monovalent (e.g., methyl), divalent (e.g., methylene), or polyvalent (e.g., methine). Examples of C1-C3 alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (including n-propyl and isopropyl), etc.

[0032] The term "aryl" refers to an all-carbon monocyclic or fused-ring polycyclic aromatic group with a conjugated π-electron system; an aryl group can have 6 to 10 carbon atoms in one or more rings. Most commonly, an aryl group has 6 carbon atoms in the ring. For example, C6-C 10 Aryl groups are aromatic groups containing 6 to 10 carbon atoms, such as phenyl or naphthyl.

[0033] The term "5- to 6-membered heteroaryl" refers to a cyclic group with a conjugated π-electron system consisting of 5 to 6 ring atoms, where 1, 2, 3, or 4 ring atoms are heteroatoms independently selected from O, S, and N, and the remainder are carbon atoms. 5- to 6-membered heteroaryls can be attached to the rest of the molecule via heteroatoms or carbon atoms, and include 5-membered and 6-membered heteroaryls, etc. Examples of the 5- to 6-membered heteroaryl groups include, but are not limited to, pyrrole (including N-pyrrole, 2-pyrrole, and 3-pyrrole), pyrazolyl (including 2-pyrazolyl and 3-pyrazolyl), imidazole (including N-imidazolyl, 2-imidazolyl, 4-imidazolyl, and 5-imidazolyl), oxazolyl (including 2-oxazolyl, 4-oxazolyl, and 5-oxazolyl), and triazolyl (1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl). And 4H-1,2,4-triazolyl), tetrazolyl, isoxazolyl (including 3-isooxazolyl, 4-isooxazolyl and 5-isooxazolyl, etc.), thiazolyl (including 2-thiazolyl, 4-thiazolyl and 5-thiazolyl, etc.), furanyl (including 2-furanyl and 3-furanyl, etc.), thiophene (including 2-thiophene and 3-thiophene, etc.), pyridyl (including 2-pyridyl, 3-pyridyl and 4-pyridyl, etc.), pyrazinyl, pyrimidinyl (including 2-pyrimidinyl and 4-pyrimidinyl, etc.), etc.

[0034] The beneficial effects of this invention are:

[0035] (1) The raw materials and reagents used in the synthesis method of the 2-aryl-4-phosphono-4H-chromene compound of the present invention are readily available and inexpensive; and the various raw materials can be conveniently stored at room temperature without strict special treatment, making them easy to manage and highly safe.

[0036] (2) The reaction conditions of the method of the present invention are mild and easy to operate. It has high compatibility with various functional groups in the substrate, a wide range of substrates, and high synthesis efficiency. Moreover, the only byproduct is water, which has high atom economy and is green and environmentally friendly.

[0037] (3) The compounds obtained by this invention are a class of multifunctional compounds containing both 4H-chromene and phosphonoyl substituents. They are important organic synthetic compounds that can provide more candidate molecules and lead compounds for the development of new drugs and drug screening. Detailed Implementation

[0038] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Furthermore, unless otherwise specified, all reagents used in the following embodiments are commercially available or can be synthesized according to methods described herein or known to the public. Reaction conditions not listed are also readily available to those skilled in the art.

[0039] The general synthetic formula for generating 2-aryl-4-phosphono-4H-chromene compounds in this invention is as follows:

[0040]

[0041] Example 1: Synthesis of 2-phenyl-4-(diphenylphosphono)-4H-chromene

[0042]

[0043] Under air atmosphere, (E)-3-(2-hydroxyphenyl)-1-phenyl-2-propen-1-one (67.2 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred. The reaction was monitored by TLC. After the starting material was completely eliminated, the reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a yellow solid, which was the product 2-phenyl-4-(diphenylphosphinoyl)-4H-chromene, with a yield of 76% and a melting point of 181-183 °C.

[0044] 1H NMR(600MHz,CDCl3):δ=7.73-7.69(m,4H),7.56-7.54(m,1H),7.49-7.45(m,5H),7.36-7.32(m,5H),7.16-7.11(m,2H),6.93(t,J=7.8Hz,1H),6.86(d,J=8.4Hz,1H),5.39(dd,J=5.4Hz,3.6Hz,1H),4.66(dd,J=21.0Hz,5.4Hz,1H); 13 C{ 1 H}NMR(150MHz,CDCl3):δ=152.0(d,J C-P =4.5Hz),151.1(d,J C-P =9.0Hz),133.6(d,J C-P =3.0Hz),132.09(d,J C-P =3.0Hz),132.06(d,J C-P =1.5Hz),132.02,131.98(d,J C-P =4.5Hz),130.3(d,J C-P =94.5Hz),129.8(d,J C-P =94.5Hz),129.6(d,J C-P =3.0Hz),128.9,128.6(d,J C-P =3.0Hz),128.5(J C-P =12.0Hz),128.3,128.2(d,J C-P =12.0Hz),124.8,123.6(d,J C-P =1.5Hz),116.5(d,J C-P =1.5Hz),116.0(d,J C-P =3.0Hz),92.8(d,J C-P =6.0Hz),40.6(d,J C-P =67.5Hz); 31 P{ 1 H}NMR(243MHz,CDCl3):δ=30.6;HRMS(ESI):Exact mass calcd for C 27 H 21 O2P[M+H] + :409.1352,Found:409.1340。

[0045] Example 2: Synthesis of 5-methoxy-2-phenyl-4-(diphenylphosphono)-4H-chromene

[0046]

[0047] Under air atmosphere, (E)-3-(2-hydroxy-6-methoxyphenyl)-1-phenyl-2-propen-1-one (76.2 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred until the starting material was completely dissolved. The reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a yellow oily liquid, which was the product 5-methoxy-2-phenyl-4-(diphenylphosphino)-4H-chromene, with a yield of 54%.

[0048] 1 H NMR (600MHz, CDCl3): δ=7.81-7.78(m,2H),7.67-7.64(m,2H),7.51-7.49(m,1H),7.44-7.41(m,5H),7.35-7.32(m,2H),7.285-7.275(m,3H), 7.18-7.15(m,1H),6.69(d,J=8.4Hz,1H),6.37(d,J=7.8Hz,1H),5.50(dd,J=5.4Hz,3.0Hz,1H),4.90(dd,J=15.6Hz,6.0Hz,1H),3.16(s,3H); 13 C{ 1 H}NMR (150MHz, CDCl3): δ = 156.5 (d, J C-P =3.0Hz), 154.0(d,J C-P =4.5Hz), 152.0(d,J C-P =9.0Hz), 133.6(d,J C-P =4.5Hz), 132.0(d,J C-P =91.5Hz), 131.8(d,J) C-P =1.5Hz), 131.7, 131.45 (d, J) C-P =6.0Hz), 131.44(d,J C-P =91.5Hz),131.4,128.71,128.67(d,J C-P =3.0Hz), 128.1, 128.0 (d, J) C-P=12.0Hz), 127.8(d,J) C-P =10.5Hz), 125.0(d,J) C-P =1.5Hz), 109.3(d,J C-P =1.5Hz), 106.0(d,J C-P =4.5Hz), 104.9(d,J C-P =1.5Hz), 93.6(d,J C-P =7.5Hz), 54.6, 36.7 (d, J) C-P =67.5Hz); 31 P{ 1 H}NMR (243MHz, CDCl3): δ = 29.2; HRMS (ESI): Exact mass calcd for C 28 H 23 O3P[M+H] + :439.1458,Found:439.1446.

[0049] Example 3: Synthesis of 6-methoxy-2-phenyl-4-(diphenylphosphono)-4H-chromene

[0050]

[0051] Under air atmosphere, (E)-3-(2-hydroxy-5-methoxyphenyl)-1-phenyl-2-propen-1-one (76.2 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred until the starting material was completely dissolved. The reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a brown solid, which was the product 6-methoxy-2-phenyl-4-(diphenylphosphino)-4H-chromene, with a yield of 67% and a melting point of 134-136 °C.

[0052] 1H NMR(600MHz,CDCl3):δ=7.76-7.69(m,4H),7.56-7.54(m,1H),7.51-7.49(m,1H),7.48-7.44(m,4H),7.40-7.37(m,2H),7.34-7.31(m,3H),6.82(d,J=9.0Hz,1H),6.72-6.70(m,1H),6.53-6.52(m,1H),5.37(dd,J=5.4Hz,3.0Hz,1H),4.64(dd,J=20.4Hz,5.4Hz,1H),3.56(s,3H); 13 C{ 1 H}NMR(150MHz,CDCl3):δ=155.3(d,J C-P =3.0Hz),151.3(d,J C-P =9.0Hz),146.1(d,J C-P =4.5Hz),133.7(d,J C-P =3.0Hz),132.1(d,J C-P =4.5Hz),132.0(d,J C-P =9.0Hz),130.3(d,J C-P =93.0Hz),130.1(d,J C-P =93.0Hz),128.8,128.5(d,J C-P =10.5Hz),128.30(d,J C-P =10.5Hz),128.28,124.8(d,J C-P =1.5Hz),117.4(d,J C-P =3.0Hz),116.4(d,J C-P =4.5Hz),115.6(d,J C-P =3.0Hz),112.8(d,J C-P =3.0Hz),91.7(d,J C-P =7.5Hz),55.5,41.1(d,J C-P =67.5Hz); 31 P{ 1 H}NMR(243MHz,CDCl3):δ=30.5;HRMS(ESI):Exact mass calcd for C 28 H 23 O3P[M+H] + :439.1458,Found:439.1450。

[0053] Example 4: Synthesis of 6-chloro-2-phenyl-4-(diphenylphosphono)-4H-chromene

[0054]

[0055] Under air atmosphere, (E)-3-(5-chloro-2-hydroxyphenyl)-1-phenyl-2-propen-1-one (77.4 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred. The reaction was monitored by TLC. After the starting material was completely eliminated, the reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a green solid, which was the product 6-chloro-2-phenyl-4-(diphenylphosphino)-4H-chromene, with a yield of 66% and a melting point of 180-182 °C.

[0056] 1 H NMR (600MHz, CDCl3): δ=7.74-7.71(m,4H),7.59-7.57(m,1H),7.54-7.44(m,5H),7.41-7.38(m,2H),7.34-7.32(m,3H),7.11-7.10(d t,J=8.4Hz,2.4Hz,1H),7.00(t,J=1.8Hz,1H),6.81(d,J=8.4Hz,1H),5.36(dd,J=4.8Hz,3.0Hz,1H),4.58(dd,J=19.8Hz,4.8Hz,1H); 13 C{ 1 H}NMR (150MHz, CDCl3): δ = 151.1 (d, J C-P =9.0Hz), 150.7(d,J C-P =4.5Hz), 133.2(d,J C-P =3.0Hz), 132.3(d,J C-P =3.0Hz), 132.2(d,J C-P =3.0Hz), 132.0(d,J C-P =9.0Hz), 131.9(d,J C-P =9.0Hz), 130.01(d,J C-P =96.0Hz), 129.4(d,J) C-P =96.0Hz), 129.2(d,J C-P =3.0Hz),129.1,128.7,128.6(d,JC-P =4.5Hz),128.4,128.3,128.2(d,J C-P =3.0Hz), 124.7, 117.8 (d, J) C-P =4.5Hz), 117.7(d,J) C-P =1.5Hz), 92.4(d,J C-P =7.5Hz), 40.7(d,J C-P =67.5Hz); 31 P{ 1 H}NMR (243MHz, CDCl3): δ = 30.1; HRMS (ESI): Exact mass calcdfor C 27 H 20 ClO2P[M+H] + :443.0962,Found:443.0953.

[0057] Example 5: Synthesis of 7-methyl-2-phenyl-4-(diphenylphosphono)-4H-chromene

[0058]

[0059] Under air atmosphere, (E)-3-(2-hydroxy-4-methylphenyl)-1-phenyl-2-propen-1-one (71.4 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred. The reaction was monitored by TLC. After the starting material was completely eliminated, the reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a yellow solid, which was the product 7-methyl-2-phenyl-4-(diphenylphosphino)-4H-chromene, with a yield of 85% and a melting point of 189-191 °C.

[0060] 1 H NMR (600MHz, CDCl3): δ=7.73-7.70(m,4H),7.56-7.54(m,1H),7.50-7.44(m,5H),7.38-7.32(m,5H),6.95(dd,J=7 .2Hz,1.8Hz,1H),6.74-6.72(m,2H),5.39(dd,J=4.8Hz,3.6Hz,1H),4.63(dd,J=20.4Hz,5.4Hz,1H),2.27(s,3H); 13 C{ 1H}NMR (150MHz, CDCl3): δ = 151.9 (d, J C-P =3.0Hz), 151.1(d,J C-P =9.0Hz), 138.8(d,J) C-P =3.0Hz), 133.7(d,J C-P =3.0Hz), 132.1(d,J C-P =9.0Hz), 132.0(d,J C-P =9.0Hz), 131.9(d,J C-P =1.5Hz), 130.5(d,J C-P =94.5Hz), 130.1(d,J C-P =94.5Hz), 129.3(d,J) C-P =3.0Hz), 128.8, 128.5 (d, J) C-P =10.5Hz), 128.3, 128.2 (d, J) C-P =12.0Hz), 124.8(d,J) C-P =1.5Hz), 124.5(d,J C-P =1.5Hz), 117.0(d,J C-P =3.0Hz), 112.8(d,J C-P =4.5Hz), 92.9(d,J C-P =6.0Hz), 40.4(d,J C-P =69.0Hz), 21.1; 31 P{ 1 H}NMR (243MHz, CDCl3): δ = 30.3; HRMS (ESI): Exact mass calcd forC 28 H 23 O2P[M+H] + :423.1508,Found:423.1498.

[0061] Example 6: Synthesis of 7-nitro-2-phenyl-4-(diphenylphosphono)-4H-chromene

[0062]

[0063] Under air atmosphere, (E)-3-(2-hydroxy-4-nitrophenyl)-1-phenyl-2-propen-1-one (80.7 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred until the starting material was completely dissolved. The reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a yellow solid, which was the product 7-nitro-2-phenyl-4-(diphenylphosphino)-4H-chromene, with a yield of 55% and a melting point of 165-167 °C.

[0064] 1 H NMR (600MHz, CDCl3): δ=7.81-7.76(m,3H),7.71-7.68(m,3H),7.63-7.60(m,1H),7.54-7.50(m,3H), 7.46-7.45(m,2H),7.39-7.35(m,6H),5.34(dd,J=5.4Hz,3.6Hz,1H),4.71(dd,J=21.0Hz,5.4Hz,1H); 13 C{ 1 H}NMR (150MHz, CDCl3): δ = 152.3 (d, J C-P =4.5Hz), 151.1(d,J C-P =9.0Hz), 148.0(d,J C-P =1.5Hz), 132.6(d,J C-P =3.0Hz), 132.5(d,J C-P =3.0Hz), 132.1(d,J C-P =7.5Hz), 131.8(d,J C-P =9.0Hz), 130.4(d,J C-P =3.0Hz), 129.9(d,J C-P =96.0Hz), 129.5, 128.9 (d, J) C-P =10.5Hz),128.63,128.55,128.5(d,J C-P =96.0Hz), 128.4(d,J) C-P =10.5Hz), 124.7, 123.9 (d, J) C-P =6.0Hz), 118.2(d,J C-P =1.5Hz), 111.8(d,J C-P=1.5Hz), 92.6(d,J C-P =7.5Hz), 40.9(d,J C-P =66.0Hz); 31 P{ 1 H}NMR (243MHz, CDCl3): δ = 30.8; HRMS (ESI): Exact mass calcd for C 27 H 20 NO4P[M+H] + :454.1203,Found:454.1196.

[0065] Example 7: Synthesis of 8-methoxy-2-phenyl-4-(diphenylphosphono)-4H-chromene

[0066]

[0067] Under air atmosphere, (E)-3-(2-hydroxy-3-methoxyphenyl)-1-phenyl-2-propen-1-one (76.2 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred. The reaction was monitored by TLC. After the starting material was completely eliminated, the reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a yellow solid, which was the product 8-methoxy-2-phenyl-4-(diphenylphosphino)-4H-chromene, with a yield of 56% and a melting point of 99-101 °C.

[0068] 1 H NMR (600MHz, CDCl3): δ=7.74-7.71(m,4H),7.57-7.54(m,1H),7.53-7.51(m,2H),7.49-7.45(m,3H),7.37-7.31(m,5H),6.88-6.85 (m,1H),6.77(d,J=8.4Hz,1H),6.72(d,J=7.8Hz,1H),5.38(dd,J=5.4Hz,3.6Hz,1H),4.67(dd,J=21.0Hz,5.4Hz,1H),3.81(s,3H); 13 C{ 1 H}NMR (150MHz, CDCl3): δ = 151.0 (d, J C-P =9.0Hz), 148.1(d,J C-P =1.5Hz), 142.0(d,JC-P =4.5Hz), 133.6(d,J C-P =3.0Hz), 132.1(d,J C-P =3.0Hz), 132.04(d,J C-P =4.5Hz), 131.98(d,J C-P =4.5Hz), 130.3(d,J C-P =94.5Hz), 129.9(d,J) C-P =94.5Hz), 128.9, 128.5 (d, J) C-P =12.0Hz), 128.4, 128.2 (d, J) C-P =10.5Hz),124.9,123.2,121.4(d,J C-P =3.0Hz), 117.0(d,J C-P =4.5Hz), 111.8, 92.8 (d, J) C-P =6.0Hz), 56.4, 40.8 (d, J) C-P =67.5Hz); 31 P{ 1 H}NMR (243MHz, CDCl3): δ = 31.1; HRMS (ESI): Exact mass calcd for C 28 H 23 O3P[M+H] + :439.1458,Found:439.1451.

[0069] Example 8: Synthesis of 2-(2-chlorophenyl)-4-(diphenylphosphono)-4H-chromene

[0070]

[0071] Under air atmosphere, (E)-1-(2-chlorophenyl)-3-(2-hydroxyphenyl)-2-propen-1-one (77.4 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred until the starting material was completely eliminated. The reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a green oily liquid, which was the product 2-(2-chlorophenyl)-4-(diphenylphosphino)-4H-chromene, with a yield >99%.

[0072] 1H NMR(600MHz,CDCl3):δ=7.80-7.77(m,2H),7.72-7.69(m,2H),7.56-7.54(m,1H),7.52-7.50(m,1H),7.48-7.45(m,2H),7.42-7.39(m,2H),7.35-7.33(m,1H),7.26-7.21(m,3H),7.16-7.13(m,1H),7.06(d,J=7.8Hz,1H),6.94-6.92(m,1H),6.81(d,J=8.4Hz,1H),5.32(dd,J=4.8Hz,3.0Hz,1H),4.70(dd,J=21.0Hz,4.8Hz,1H); 13 C{ 1 H}NMR(150MHz,CDCl3):δ=152.2(d,J C-P =4.5Hz),149.9(d,J C-P =7.5Hz),133.4(d,J C-P =3.0Hz),132.7(d,J C-P =1.5Hz),132.2(d,J C-P =6.0Hz),132.12(d,J C-P =6.0Hz),132.06(d,J C-P =1.5Hz),130.39(d,J C-P =3.0Hz),130.36,130.12(d,J C-P =96.0Hz),130.11(d,J C-P =15.0Hz),130.0(d,J C-P =96.0Hz),129.6(d,J C-P =3.0Hz),128.7(d,J C-P =3.0Hz),128.4(d,J C-P =30.0Hz),128.3(d,J C-P =30.0Hz),126.6,123.7(d,J C-P =1.5Hz),116.5(d,J C-P =1.5Hz),116.0(d,J C-P =3.0Hz),98.3(d,J C-P =7.5Hz),40.9(d,J C-P =67.5Hz); 31 P{ 1H}NMR (243MHz, CDCl3): δ = 30.7; HRMS (ESI): Exact mass calcd for C 27 H 20 ClO2P[M+H] + :443.0962,Found:443.0953.

[0073] Example 9: Synthesis of 2-(3-methoxyphenyl)-4-(diphenylphosphono)-4H-chromene

[0074]

[0075] Under air atmosphere, (E)-3-(2-hydroxyphenyl)-1-(3-methoxyphenyl)-2-propen-1-one (76.2 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred until the starting material was completely dissolved. The reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a yellow oily liquid, which was the product 2-(3-methoxyphenyl)-4-(diphenylphosphinoyl)-4H-chromene, with a yield of 55%.

[0076] 1 H NMR (600MHz, CDCl3): δ=7.73-7.68(m,4H),7.56-7.55(m,1H),7.49-7.45(m,3H) ,7.37-7.34(m,2H),7.24(t,J=8.4Hz,1H),7.14(t,J=7.8Hz,1H),7.10(d,J=7.2H z,1H),7.05(d,J=7.8Hz,1H),7.01(s,1H),7.93(t,J=7.2Hz,1H),6.88-6.85(m, 2H), 5.38 (dd, J = 5.4Hz, 3.6Hz, 1H), 4.68 (dd, J = 21.0Hz, 5.4Hz, 1H), 3.80 (s, 3H); 13 C{ 1 H}NMR (150MHz, CDCl3): δ = 159.6, 152.0 (d, J C-P =3.0Hz), 150.9(d,J C-P =9.0Hz), 135.0(d,J C-P =3.0Hz), 132.06(d,J C-P=13.5Hz), 132.02(d,J C-P =13.5Hz), 130.4(d,J C-P =94.5Hz), 129.8(d,J) C-P =94.5Hz), 129.6(d,J) C-P =1.5Hz),129.4,128.6,128.5(d,J C-P =10.5Hz), 128.2(d,J C-P =12.0Hz),123.6,117.3,116.5,116.0(d,J C-P =4.5Hz),114.3,110.6,93.2(d,J C-P =6.0Hz), 55.3, 40.7 (d, J) C-P =67.5Hz); 31 P{ 1 H}NMR (243MHz, CDCl3): δ = 31.6; HRMS (ESI): Exact mass calcd for C 28 H 23 O3P[M+H] + :439.1458,Found:439.1456.

[0077] Example 10: Synthesis of 2-(3-chlorophenyl)-4-(diphenylphosphono)-4H-chromene

[0078]

[0079] Under air atmosphere, (E)-1-(3-chlorophenyl)-3-(2-hydroxyphenyl)-2-propen-1-one (77.4 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred until the starting material was completely eliminated. The reaction was continued for 24 h. After cooling to room temperature, the solvent was removed under reduced pressure, and the product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1). A yellow oily liquid was obtained, which was the product 2-(3-chlorophenyl)-4-(diphenylphosphinoyl)-4H-chromene, with a yield >99%.

[0080] 1H NMR(600MHz,CDCl3):δ=7.71-7.66(m,4H),7.57-7.55(m,1H),7.52-7.49(m,1H),7.47-7.44(m,3H),7.39-7.36(m,2H),7.34-7.33(m,1H),7.29-7.28(m,1H),7.26-7.23(m,1H),7.17-7.14(m,1H),7.03-7.02(m,1H),6.93-6.91(m,1H),6.87(d,J=7.8Hz,1H),5.43(dd,J=4.8Hz,3.0Hz,1H),4.65(dd,J=19.8Hz,5.4Hz,1H); 13 C{ 1 H}NMR(150MHz,CDCl3):δ=151.9(d,J C-P =4.5Hz),149.9(d,J C-P =9.0Hz),135.3(d,J C-P =3.0Hz),134.4,132.2(d,J C-P =1.5Hz),132.1(d,J C-P =3.0Hz),132.0(d,J C-P =9.0Hz),130.0(d,J C-P =94.5Hz),129.8(d,J C-P =94.5Hz),129.59,129.57,128.9,128.7(d,J C-P =3.0Hz),128.44(d,J C-P =39.0Hz),128.36(d,J C-P =39.0Hz),124.9,123.7(d,J C-P =1.5Hz),122.9(d,J C-P =1.5Hz),116.5(d,J C-P =1.5Hz),115.9(d,J C-P =4.5Hz),94.0(d,J C-P =6.0Hz),40.6(d,J C-P =67.5Hz); 31 P{ 1 H}NMR(243MHz,CDCl3):δ=30.6;HRMS(ESI):Exact mass calcd forC 27 H 20 ClO2P[M+H] +:443.0962,Found:443.0956.

[0081] Example 11: Synthesis of 2-(4-methylphenyl)-4-(diphenylphosphono)-4H-chromene

[0082]

[0083] Under air atmosphere, (E)-3-(2-hydroxyphenyl)-1-(4-methylphenyl)-2-propen-1-one (71.4 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred. The reaction was monitored by TLC. After the starting material was completely eliminated, the reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a yellow solid, which was the product 2-(4-methylphenyl)-4-(diphenylphosphino)-4H-chromene, with a yield of 50% and a melting point of 195-197 °C.

[0084] 1 H NMR (600MHz, CDCl3): δ=7.72-7.70(m,4H),7.56-7.54(m,1H),7.49-7.45(m,3H),7.37-7.33(m,4H),7.16-7.12(m,4H) ,6.94-6.91(m,1H),6.85(d,J=7.8Hz,1H),5.33(dd,J=5.4Hz,3.0Hz,1H),4.65(dd,J=20.4Hz,5.4Hz,1H),2.35(s,3H); 13 C{ 1 H}NMR (150MHz, CDCl3): δ = 152.1 (d, J C-P =4.5Hz), 151.2(d,J C-P =9.0Hz), 138.9, 132.1 (d, J) C-P =7.5Hz), 132.04(d,J C-P =3.0Hz), 131.97, 131.95 (d, J) C-P =3.0Hz), 130.8(d,J C-P =3.0Hz), 130.4(d,J C-P =94.5Hz), 129.8(d,J) C-P =94.5Hz), 129.6(d,J) C-P=3.0Hz), 129.0, 128.6 (d, J) C-P =3.0Hz), 128.5(d,J C-P =10.5Hz), 128.1(d,J C-P =10.5Hz), 124.7, 123.5 (d, J) C-P =3.0Hz), 116.5(d,J C-P =1.5Hz), 116.0(d,J C-P =4.5Hz), 91.9(d,J C-P =7.5Hz), 40.6(d,J C-P =67.5Hz), 21.3; 31 P{ 1 H}NMR (243MHz, CDCl3): δ = 30.6; HRMS (ESI): Exact mass calcd forC 28 H 23 O2P[M+H] + :423.1508,Found:423.1498.

[0085] Example 12: Synthesis of 2-(4-bromophenyl)-4-(diphenylphosphono)-4H-chromene

[0086]

[0087] Under air atmosphere, (E)-1-(4-bromophenyl)-3-(2-hydroxyphenyl)-2-propen-1-one (90.6 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred. The reaction was monitored by TLC. After the starting material was completely eliminated, the reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a white solid, which was the product 2-(4-bromophenyl)-4-(diphenylphosphino)-4H-chromene, with a yield of 75% and a melting point of 191-193 °C.

[0088] 1H NMR (600MHz, CDCl3): δ=7.71-7.66(m,4H),7.56-7.54(m,1H),7.51-7.48(m,1H),7.46-7.44(m,4H),7.38-7.35(m,2H),7.34-7.32(m,2H),7.16- 7.14(m,1H),7.02(d,J=7.8Hz,1H),6.92(t,J=7.8Hz,1H),6.85(d,J=7.8Hz,1H),5.41(dd,J=4.8Hz,3.0Hz,1H),4.64(dd,J=19.8Hz,4.8Hz,1H); 13 C{ 1 H}NMR (150MHz, CDCl3): δ = 151.9 (d, J C-P =3.0Hz), 151.2(d,J C-P =9.0Hz), 132.4(d,J C-P =3.0Hz),132.1,132.04,131.98(d,J C-P =3.0Hz), 131.5, 130.0(d,J) C-P =94.5Hz), 129.9(d,J) C-P =94.5Hz),129.6,128.7,128.5(d,J C-P =10.5Hz), 128.2(d,J C-P =10.5Hz),126.3,123.7,123.0,116.5,115.9(d,J C-P =4.5Hz), 93.3(d,J C-P =6.0Hz), 40.6(d,J C-P =67.5Hz); 31 P{ 1 H}NMR (243MHz, CDCl3): δ = 31.1; HRMS (ESI): Exact mass calcd for C 27 H 20 BrO2P[M+H] + :487.0457,Found:487.0447.

[0089] Example 13: Synthesis of 2-(2-naphthyl)-4-(diphenylphosphono)-4H-chromene

[0090]

[0091] Under air atmosphere, (E)-3-(2-hydroxyphenyl)-1-(2-naphthyl)-2-propen-1-one (82.2 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred. The reaction was monitored by TLC. After the starting material was completely eliminated, the reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a brown oily liquid, which was the product 2-(2-naphthyl)-4-(diphenylphosphino)-4H-chromene, with a yield of 40%.

[0092] 1 H NMR (600MHz, CDCl3): δ = 8.01 (s, 1H), 7.86-7.84 (m, 1H), 7.82-7.80 (m, 1H), 7.7 8-7.77(m,1H),7.75-7.72(m,4H),7.57-7.55(m,1H),7.53-7.51(m,1H),7.50-7 .46(m,5H),7.37-7.34(m,2H),7.18(t,J=7.8Hz,1H),7.12(d,J=7.8Hz,1H),6. 96-6.94(m,2H),5.56(dd,J=5.4Hz,3.6Hz,1H),4.71(dd,J=20.4Hz,5.4Hz,1H); 13 C{ 1 H}NMR (150MHz, CDCl3): δ = 152.1 (d, J C-P =3.0Hz), 151.0(d,J C-P =9.0Hz),133.4,133.0,132.1(d,J C-P =9.0Hz), 132.0(d,J C-P =3.0Hz), 130.6(d,J C-P =3.0Hz), 130.1(d,J C-P =94.5Hz), 129.8(d,J) C-P =96.0Hz), 129.6(d,J) C-P =3.0Hz), 128.7(d,J C-P =1.5Hz), 128.54, 128.46 (d, J) C-P =1.5Hz), 128.2(d,J C-P =10.5Hz),128.0,127.6,126.5(d,J C-P=15.0Hz), 124.0, 123.6 (d, J) C-P =3.0Hz), 122.3, 116.5 (d, J) C-P =3.0Hz), 116.1(d,J C-P =4.5Hz), 93.4(d,J C-P =6.0Hz), 40.8(d,J C-P =67.5Hz); 31 P{ 1 H}NMR (243MHz, CDCl3): δ = 31.3; HRMS (ESI): Exact masscalcd for C 31 H 23 O2P[M+H] + :459.1508,Found:459.1500.

[0093] Example 14: Synthesis of 2-(2-furanyl)-4-(diphenylphosphono)-4H-chromene

[0094]

[0095] Under air atmosphere, (E)-1-(2-furanyl)-3-(2-hydroxyphenyl)-2-propen-1-one (64.2 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred. The reaction was monitored by TLC. After the starting material was completely eliminated, the reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a yellow solid, which was the product 2-(2-furanyl)-4-(diphenylphosphinoyl)-4H-chromene, with a yield of 76% and a melting point of 187-189 °C.

[0096] 1H NMR(600MHz,CDCl3):δ=7.75-7.72(m,2H),7.70-7.67(m,2H),7.57-7.55(m,1H),7.49-7.46(m,3H),7.36-7.32(m,3H),7.14-7.12(m,2H),6.94-6.91(m,1H),6.82-6.81(m,1H),6.50(d,J=3.6Hz,1H),6.39(dd,J=3.0Hz,1.8Hz,1H),5.43(dd,J=5.4Hz,3.0Hz,1H),4.62(dd,J=20.4Hz,5.4Hz,1H); 13 C{ 1 H}NMR(150MHz,CDCl3):δ=151.6(d,J C-P =3.0Hz),148.0(d,J C-P =4.5Hz),144.0(d,J C-P =9.0Hz),142.8,132.1,132.03(d,J C-P =3.0Hz),131.95(d,J C-P =3.0Hz),130.6(d,J C-P =94.5Hz),129.8(d,J C-P =3.0Hz),129.7(d,J C-P =96.0Hz),128.62,128.56(d,J C-P =10.5Hz),128.1(d,J C-P =10.5Hz),123.6(d,J C-P =3.0Hz),116.4(d,J C-P =3.0Hz),116.0(d,J C-P =4.5Hz),111.2,107.3(d,J C-P =1.5Hz),91.6(d,J C-P =7.5Hz),39.9(d,J C-P =69.0Hz); 31 P{ 1 H}NMR(243MHz,CDCl3):δ=30.2;HRMS(ESI):Exact mass calcd for C 25 H 19 O3P[M+H] + :399.1145,Found:399.1135。

[0097] Example 15: Synthesis of 2-phenyl-4-[bis(2-methylphenyl)phosphono]-4H-chromene

[0098]

[0099] Under air atmosphere, (E)-3-(2-hydroxyphenyl)-1-phenyl-2-propen-1-one (67.2 mg, 0.3 mmol), bis(2-methylphenyl)phosphine oxide (82.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred until the starting material was completely dissolved. The reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent. A yellow solid was obtained, which was the product 2-phenyl-4-[bis(2-methylphenyl)phosphono]-4H-chromene, with a yield of 74% and a melting point of 142-144 °C.

[0100] 1 H NMR (600MHz, CDCl3): δ=7.62-7.59(m,1H),7.47-7.42(m,3H),7.36-7.27(m,6H),7.26-7.20(m,3H),7.12-7.10(m ,1H),7.01-6.94(m,3H),5.49(dd,J=5.4Hz,3.0Hz,1H),4.80(dd,J=18.0Hz,5.4Hz,1H),2.32(s,3H),2.16(s,3H); 13 C{ 1 H}NMR (150MHz, CDCl3): δ = 152.5 (d, J C-P =3.0Hz), 151.5(d,J C-P =9.0Hz), 143.7(d,J) C-P =7.5Hz), 143.4(d,J C-P =6.0Hz), 133.6(d,J C-P =3.0Hz), 132.3(d,J C-P =10.5Hz), 132.0(d,J C-P =10.5Hz), 131.8(d,J) C-P =3.0Hz), 131.5(d,J C-P =3.0Hz), 131.0(d,J C-P =10.5Hz), 130.7(d,J) C-P =91.5Hz), 130.6(d,J) C-P=3.0Hz).128.8,128.6(d,J) C-P =3.0Hz), 128.2, 125.4 (d, J) C-P =12.0Hz), 124.8, 124.5 (d, J) C-P =12.0Hz), 123.5(d,J C-P =1.5Hz), 116.3(d,J C-P =1.5Hz), 116.0(d,J C-P =4.5Hz), 93.6(d,J C-P =7.5Hz), 40.3(d,J C-P =67.5Hz), 21.4(d,J C-P =4.5Hz), 21.0(d,J C-P =3.0Hz); 31 P{ 1 H}NMR (243MHz, CDCl3): δ = 36.1; HRMS (ESI): Exactmass calcd for C 29 H 25 O2P[M+H] + :437.1665,Found:437.1663.

[0101] Example 16: Synthesis of 2-phenyl-4-[bis(3-methoxyphenyl)phosphono]-4H-chromene

[0102]

[0103] Under air atmosphere, (E)-3-(2-hydroxyphenyl)-1-phenyl-2-propen-1-one (67.2 mg, 0.3 mmol), bis(3-methoxyphenyl)phosphine oxide (94.3 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred. The reaction was monitored by TLC. After the starting material was completely eliminated, the reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a yellow oily liquid, which was the product 2-phenyl-4-[bis(3-methoxyphenyl)phosphono]-4H-chromene, with a yield of 63%.

[0104] 1H NMR(600MHz,CDCl3):δ=7.70-7.66(m,1H),7.50-7.42(m,4H),7.40-7.38(m,1H),7.30-7.27(m,3H),7.24-7.23(m,1H),7.05-7.02(m,1H),6.97-6.92(m,3H),6.88-6.87(m,1H),6.81-6.78(m,1H),6.75(dd,J=8.4Hz,5.4Hz,1H),5.54(t,J=4.8Hz,1H),5.12(dd,J=25.2Hz,4.8Hz,1H),3.76(s,3H),3.54(s,3H); 13 C{ 1 H}NMR(150MHz,CDCl3):δ=160.7(d,J C-P =3.0Hz),160.2(d,J C-P =3.0Hz),151.6,149.6(d,J C-P =15.0Hz),135.7(d,J C-P =4.5Hz),134.8(d,J C-P =7.5Hz),134.3(d,J C-P =3.0Hz),133.6(d,J C-P =21.0Hz),129.4(d,J C-P =3.0Hz),128.4,128.2,127.9,124.6,123.0,120.8(d,J C-P =10.5Hz),120.6(d,J C-P =10.5Hz),119.6(d,J C-P =94.5Hz),118.3(d,J C-P =94.5Hz),117.6(d,J C-P =4.5Hz),116.0,110.6(d,J C-P =6.0Hz),109.9(d,J C-P =6.0Hz),94.6,55.5,55.1,41.6(d,J C-P =70.5Hz); 31 P{ 1 H}NMR(243MHz,CDCl3):δ=39.6;HRMS(ESI):Exact mass calcd forC 29 H 25 O4P[M+H] +:469.1563,Found:469.1558.

[0105] Example 17: Synthesis of 2-phenyl-4-[bis(3-chlorophenyl)phosphono]-4H-chromene

[0106]

[0107] Under air atmosphere, (E)-3-(2-hydroxyphenyl)-1-phenyl-2-propen-1-one (67.2 mg, 0.3 mmol), bis(3-chlorophenyl)phosphine oxide (97.2 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred until the starting material was completely dissolved. The reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a yellow solid, which was the product 2-phenyl-4-[bis(3-chlorophenyl)phosphono]-4H-chromene, with a yield of 48% and a melting point of 138-140 °C.

[0108] 1 H NMR (600MHz, CDCl3): δ=7.68-7.65(m,2H),7.60-7.54(m,3H),7.52-7.47(m,3H),7.44-7.41(m,1H),7.38-7.35(m,3H),7.32-7.29(m,1H),7.2 1-7.19(m,1H),7.11-7.09(m,1H),6.98(t,J=7.2Hz,1H),6.92(d,J=8.4Hz,1H),5.37(dd,J=5.4Hz,3.0Hz,1H),4.65(dd,J=20.4Hz,5.4Hz,1H); 13 C{ 1 H}NMR (150MHz, CDCl3): δ = 152.0 (d, J C-P =4.5Hz), 151.9(d,J C-P =10.5Hz), 135.2(d,J) C-P =15.0Hz), 134.9(d,J) C-P =15.0Hz), 133.2(d,J C-P =3.0Hz), 132.5(d,J C-P =1.5Hz), 132.4, 132.0 (d, J) C-P =9.0Hz), 131.8(d,J C-P=9.0Hz), 131.4.130.1(d,J C-P =12.0Hz), 130.0(d,J C-P =9.0Hz), 129.9(d,J) C-P =7.5Hz), 129.7(d,J) C-P =13.5Hz), 129.5(d,J) C-P =3.0Hz), 129.2, 129.1 (d, J) C-P =3.0Hz),128.4,124.9,123.9(d,J C-P =3.0Hz), 116.7, 115.2 (d, J) C-P =4.5Hz), 91.9(d,J C-P =7.5Hz), 40.7(d,J C-P =69.0Hz); 31 P{ 1 H}NMR (243MHz, CDCl3): δ = 28.3; HRMS (ESI): Exact mass calcd forC 27 H 19 Cl2O2P[M+H] + :477.0572,Found:477.0565.

[0109] Example 18: Synthesis of 2-phenyl-4-[bis(4-isopropylphenyl)phosphono]-4H-chromene

[0110]

[0111] Under air atmosphere, (E)-3-(2-hydroxyphenyl)-1-phenyl-2-propen-1-one (67.2 mg, 0.3 mmol), bis(4-isopropylphenyl)phosphine oxide (103.0 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred. The reaction was monitored by TLC. After the starting material was completely eliminated, the reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent, yielding a yellow solid, which was the product 2-phenyl-4-[bis(4-isopropylphenyl)phosphono]-4H-chromene, with a yield of 62% and a melting point of 165-167 °C.

[0112] 1H NMR(600MHz,CDCl3):δ=7.65-7.58(m,4H),7.48-7.46(m,2H),7.34-7.30(m,5H),7.20-7.11(m,4H),6.93-6.91(m,1H),6.85(d,J=7.8Hz,1H),5.40-5.39(m,1H),4.61(dd,J=20.4Hz,5.4Hz,1H),2.96-2.88(m,2H),1.26(d,J=6.6Hz,6H),1.22(d,J=7.2Hz,6H); 13 C{ 1 H}NMR(150MHz,CDCl3):δ=153.2(d,J C-P =1.5Hz),153.1(d,J C-P =1.5Hz),152.0(d,J C-P =3.0Hz),150.8(d,J C-P =9.0Hz),133.8(d,J C-P =3.0Hz),132.13(d,J C-P =18.0Hz),132.1,129.7(d,J C-P =3.0Hz),128.8,128.4(d,J C-P =1.5Hz),128.2,127.6(d,J C-P =97.5Hz),127.0(d,J C-P =97.5Hz),126.6(d,J C-P =12.0Hz),126.3(d,J C-P =10.5Hz),124.8,123.4(d,J C-P =1.5Hz),116.4(d,J C-P =1.5Hz),116.3(d,J C-P =4.5Hz),93.3(d,J C-P =6.0Hz),40.7(d,J C-P =67.5Hz),34.2,34.1,23.74,23.68; 31 P{ 1 H}NMR(243MHz,CDCl3):δ=31.0;HRMS(ESI):Exact mass calcd for C 33 H 33 O2P[M+H] + :493.2291,Found:493.2287。

[0113] Example 19: Synthesis of 2-phenyl-4-[bis(4-chlorophenyl)phosphono]-4H-chromene

[0114]

[0115] Under air atmosphere, (E)-3-(2-hydroxyphenyl)-1-phenyl-2-propen-1-one (67.2 mg, 0.3 mmol), bis(4-chlorophenyl)phosphine oxide (97.2 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred until the starting material was completely dissolved. The reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent. A white solid, 2-phenyl-4-[bis(4-chlorophenyl)phosphono]-4H-chromene, was obtained with a yield of 59% and a melting point of 214-216 °C.

[0116] 1 H NMR (600MHz, CDCl3): δ=7.64-7.58(m,4H),7.50-7.44(m,4H),7.36-7.33(m,5H),7.21-7.16(m,1H),7.13-7.11( m,1H),6.99-6.95(m,1H),6.90(d,J=12.0Hz,1H),5.37(dd,J=7.8Hz,4.8Hz,1H),4.63(dd,J=31.2Hz,8.4Hz,1H); 13 C{ 1 H}NMR (150MHz, CDCl3): δ = 152.0 (d, J C-P =6.0Hz), 151.6(d,J C-P =15.0Hz), 139.0(d,J) C-P =4.5Hz), 138.9(d,J C-P =4.5Hz), 133.4(d,J C-P =10.5Hz), 133.3(d,J C-P =10.5Hz), 133.2, 129.6 (d, J) C-P =4.5Hz), 129.2(d,J C-P =19.5Hz),129.00,128.97,128.7(d,J C-P =18.0Hz), 128.54(d,J C-P =144.0Hz), 128.48, 128.1 (d, J)C-P =144.0Hz), 124.8(d,J) C-P =1.5Hz), 123.8(d,J C-P =3.0Hz), 116.7(d,J C-P =3.0Hz), 115.5(d,J C-P =6.0Hz), 92.1(d,J C-P =9.0Hz), 40.7(d,J C-P =103.5Hz); 31 P{ 1 H}NMR (243MHz, CDCl3): δ = 29.1; HRMS (ESI): Exact mass calcd forC 27 H 19 Cl2O2P[M+H] + :477.0572,Found:477.0565.

[0117] Example 20: Synthesis of 2-phenyl-4-[bis(2-naphthyl)phosphono]-4H-chromene

[0118]

[0119] Under air atmosphere, (E)-3-(2-hydroxyphenyl)-1-phenyl-2-propen-1-one (67.2 mg, 0.3 mmol), bis(2-naphthyl)phosphine oxide (108.7 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred until the starting material was completely dissolved. The reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent. A yellow solid was obtained, which was the product 2-phenyl-4-[bis(2-naphthyl)phosphonyl]-4H-chromene, with a yield of 57% and a melting point of 84-86 °C.

[0120] 1H NMR(600MHz,CDCl3):δ=8.75(d,J=8.4Hz,1H),8.62(d,J=8.4Hz,1H),8.04(m,J=8.4Hz,1H),7.91-7.89(m,2H),7.84-7.78(m,2H),7.67-7.63(m,1H),7.49-7.47(m,2H),7.41-7.38(m,2H),7.33-7.29(m,3H),7.26-7.24(m,4H),7.22-7.20(m,1H),7.11(t,J=7.8Hz,1H),6.90-6.88(m,1H),6.78(d,J=8.4Hz,1H),5.38-5.37(m,1H),5.13(dd,J=21.0Hz,5.4Hz,1H); 13 C{ 1 H}NMR(150MHz,CDCl3):δ=152.0(d,J C-P =4.5Hz),150.9(d,J C-P =9.0Hz),134.5(d,J C-P =7.5Hz),134.1(d,J C-P =9.0Hz),134.0(d,J C-P =7.5Hz),133.8(d,J C-P =9.0Hz),133.5(d,J C-P =3.0Hz),133.2(d,J C-P =3.0Hz),133.0(d,J C-P =1.5Hz),132.4(d,J C-P =10.5Hz),131.6(d,J C-P =10.5Hz),130.3(d,J C-P =3.0Hz),128.8(d,J C-P =12.0Hz),128.6(d,J C-P =1.5Hz),128.5,128.3(d,J C-P =91.5Hz),128.1,127.4,127.3(d,J C-P =4.5Hz),126.7(d,J C-P =67.5Hz),126.4(d,J C-P =91.5Hz),126.1,116.3(d,J C-P =1.5Hz),116.2(d,J C-P =4.5Hz),93.9(d,JC-P =6.0Hz), 41.2(d,J C-P =67.5Hz); 31 P{ 1 H}NMR (243MHz, CDCl3): δ = 38.5; HRMS (ESI): Exact mass calcd for C 35 H 25 O2P[M+H] + :509.1665,Found:509.1666.

[0121] Example 21: Synthesis of 2-phenyl-4-[bis(4-thienyl)phosphonyl]-4H-chromene

[0122]

[0123] Under air atmosphere, (E)-3-(2-hydroxyphenyl)-1-phenyl-2-propen-1-one (67.2 mg, 0.3 mmol), bis(2-thienyl)phosphine oxide (77.0 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and 6 mL of dry methyl acetate were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C and stirred until the starting material was completely dissolved. The reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation. The product was purified by column chromatography using dichloromethane / ethyl acetate (40 / 1) as the eluent. A red solid was obtained, which was the product 2-phenyl-4-[bis(4-thienyl)phosphonyl]-4H-chromene, with a yield of 79% and a melting point of 194-196 °C.

[0124] 1 H NMR (600MHz, CDCl3): δ=7.80-7.79(m,1H),7.67-7.66(m,1H),7.64-7.63(m,1 H),7.60-7.59(m,2H),7.51-7.49(m,1H),7.40-7.36(m,3H),7.31-7.30(m,1H ),7.25-7.24(m,1H),7.22-7.19(m,1H),7.10-7.09(m,1H),7.03(t,J=7.8Hz, 1H),6.91(d,J=8.4Hz,1H),5.46-5.44(m,1H),4.54(dd,J=22.8Hz,5.4Hz,1H); 13 C{ 1 H}NMR (150MHz, CDCl3): δ = 151.9 (d, J C-P =4.5Hz), 151.8(d,J C-P=10.5Hz), 137.3(d,J) C-P =9.0Hz), 136.9(d,J) C-P =9.0Hz), 134.4(d,J C-P =4.5Hz), 134.1(d,J C-P =4.5Hz), 133.6(d,J C-P =3.0Hz), 130.9(d,J C-P =106.5Hz), 130.0(d,J C-P =3.0Hz), 129.7(d,J) C-P =106.5Hz), 129.1, 129.0 (d, J) C-P =3.0Hz), 128.4, 128.3 (d, J) C-P =15.0Hz), 128.0(d,J C-P =13.5Hz), 125.0, 123.8 (d, J) C-P =3.0Hz), 116.5(d,J C-P =3.0Hz), 115.4(d,J C-P =4.5Hz), 91.7(d,J C-P =7.5Hz), 43.0(d,J C-P =76.5Hz); 31 P{ 1 H}NMR (243MHz, CDCl3): δ = 21.3; HRMS (ESI): Exact mass calcd forC 23 H 17 O2PS2[M+H] + :421.0480,Found:421.0475.

[0125] Comparative Example 1: Synthesis of 2-phenyl-4-(diphenylphosphono)-4H-chromene

[0126]

[0127] Based on the above reaction formula, nine experimental groups (1-9) were set up. The experiments in these nine groups were conducted according to the solvents and reaction times specified in Table 1. The reaction steps were as follows: Under an air atmosphere, (E)-3-(2-hydroxyphenyl)-1-phenyl-2-propen-1-one (67.2 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), mercuric trifluoromethanesulfonate (15.0 mg, 0.03 mmol), and the organic solvents listed in Table 1 were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C, stirred, and the reaction was monitored by TLC. After the starting material was completely eliminated, the reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation, and the product was purified by column chromatography to obtain 2-phenyl-4-(diphenylphosphinoyl)-4H-chromene. The yields are shown in Table 1.

[0128] Table 1

[0129]

[0130] Comparative Example 2: Synthesis of 2-phenyl-4-(diphenylphosphono)-4H-chromene

[0131]

[0132] Based on the above reaction formula, eight experimental groups (1-8) were set up. The catalysts and reaction times in each of the eight groups were specified in Table 2. The reaction steps were as follows: Under air atmosphere, (E)-3-(2-hydroxyphenyl)-1-phenyl-2-propen-1-one (67.2 mg, 0.3 mmol), diphenylphosphine oxide (72.8 mg, 0.36 mmol), the catalyst from Table 2, and dichloroethane were added to a 35.0 mL sealed tube. The mixture was heated to 80 °C, stirred, and the reaction was monitored by TLC. After the starting material was completely eliminated, the reaction was continued for 24 h. After cooling to room temperature, the solvent was removed by vacuum distillation, and the product 2-phenyl-4-(diphenylphosphinoyl)-4H-chromene was obtained by column chromatography. The yields are shown in Table 2.

[0133] Table 2

[0134]

[0135] As can be seen from Examples 1 and Comparative Examples 1-2, the optimal conditions are: methyl acetate as solvent, reaction temperature of 80°C, reaction time of 30 hours, mercuric trifluoromethanesulfonate as catalyst (0.1 times that of 2-hydroxychalcone), and diphenylphosphine oxide (1.2 times that of 2-hydroxychalcone).

Claims

1. A method for synthesizing a 2-aryl-4-phosphono-4H-chromene compound, characterized in that, The reaction includes the following steps: 2-hydroxychalcone, diarylphosphine oxide, and mercuric trifluoromethanesulfonate are dissolved in an organic solvent and reacted at 80–100 °C. After the reaction is complete, the mixture is separated and purified to obtain a 2-aryl-4-phosphono-4H-chromene compound, the general reaction formula of which is as follows: Among them, R 1 Selected from hydrogen; R 2 and R 3 Each is selected from Ph.

2. The method according to claim 1, characterized in that, The molar ratio of 2-hydroxychalcone to diarylphosphine oxide is (0.1-0.5):(0.12-0.6).

3. The method according to claim 2, characterized in that, The molar ratio of 2-hydroxychalcone to diarylphosphine oxide is 0.3:0.

36.

4. The method according to claim 1, characterized in that, The molar ratio of 2-hydroxychalcone to mercuric trifluoromethanesulfonate is (0.1–0.5):(0.01–0.05).

5. The method according to claim 4, characterized in that, The molar ratio of 2-hydroxychalcone to mercuric trifluoromethanesulfonate is 0.3:0.

03.

6. The method according to claim 5, characterized in that, The molar ratio of diarylphosphine oxide to mercuric trifluoromethanesulfonate is (0.3–0.4):(0.02–0.04).

7. The method according to claim 1, characterized in that, The organic solvent is selected from one or more of acetonitrile, toluene, dichloromethane, 1,2-dichloroethane, ethyl acetate, methyl acetate, and propyl acetate.

8. The method according to claim 7, characterized in that, The organic solvent is selected from methyl acetate.

9. The method according to claim 1, characterized in that, The volume of the organic solvent used is 20 times the molar amount of 2-hydroxychalcone.

10. The method according to claim 1, characterized in that, The reaction temperature is 80℃.

11. The method according to claim 1, characterized in that, The reaction time is 20–48 hours.

12. The method according to claim 11, characterized in that, The reaction time is 30 hours.

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