Preparation method of cyclic phosphoric acid compound and derivative thereof

Abstract

The invention provides a preparation method of a cyclic phosphoric acid compound as shown in a formula (III) or (IV) and a derivative thereof, which is an organic cyclic phosphoric acid compound and a derivative thereof directly synthesized by using white phosphorus, and the process method avoids the problems of use of chlorine with great pollution and subsequent emission in the traditional phosphorus chemical production. And the method is a more environment-friendly production method. In addition, the method disclosed by the invention is mild in reaction condition, relatively short in reaction time and simple in post-treatment, and relatively high yield can be obtained. # imgabs0 #

Description

Technical Field

[0001] The invention relates to the field of organophosphorus chemistry and chemical engineering, and in particular to a method for preparing a cyclic phosphoric acid compound containing a diaryl structural unit and a derivative thereof. Background Art

[0002] As is well known, organophosphate compounds are widely used in the fields of agriculture, medicinal chemistry, organic synthesis, etc. Regarding the synthesis method of cyclic phosphoric acid and its derivatives, it involves the synthesis of a variety of chiral phosphoric acids and their derivatives, and this type of compound has become a very common catalyst in the field of organic catalytic synthesis, because it can induce the synthesis of chiral compounds, so it occupies an important position in the field of chiral catalysis. However, the traditional synthesis method of this type of compound still needs to be obtained by the reaction of the corresponding phenol with phosphorus oxychloride and then hydrolyzed. And phosphorus oxychloride is a class of chemical reagents that is very sensitive to water and very active, so it needs to be obtained by the reaction of white phosphorus and chlorine to obtain phosphorus trichloride, and then oxidized to obtain (see non-patent literature 1). In addition, the reaction of phosphorus oxychloride with phenol will be accompanied by the generation of a large amount of acid, so it is necessary to add a large amount of alkali for neutralization, thereby also resulting in the generation of a large amount of solid hydrochloride, which will have an adverse effect on the environment. Therefore, from the perspective required by modern chemical technology, it is urgent to develop a method for synthesizing cyclic phosphoric acid compounds and their derivatives that is environmentally friendly and cost-effective, which transcends the traditional chlorine process.

[0003] Prior art literature

[0004] Non-patent literature

[0005] Non-patent literature 1: Donath, M.; Schwedtmann, K.; Schneider, T.; Hennersdorf, F.; Bauzá, A.; Frontera, A.; Weigand, J. Direct Conversion of White Phosphorus to Versatile Phosphorus Transfer Reagents via Oxidative Onioation. Nat. Chem. 2022, 14, 384-391. Summary of the invention

[0006] Technical problem to be solved by the invention

[0007] The present invention is accomplished in view of the above problems, and its object is to provide a method for synthesizing cyclic phosphate compounds containing diaryl structural units and derivatives thereof which are not only environmentally friendly but also low in cost and easy to efficiently synthesize.

[0008] Solutions for solving problems

[0009] The technical solution of the present invention is as follows:

[0010] The scheme of the present invention is a cyclic phosphoric acid compound and its derivatives, which are cyclic phosphoric acid compounds and their derivatives containing diaryl structural units as shown in the following formula (III) or (IV), characterized in that:

[0011]

[0012] In formula (III) or (IV), R 1 It can be one of hydrogen, halogen, alkenyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, alkyl, alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted biphenyl, naphthyl, anthracenyl, phenanthryl, pyridyl, thienyl, or benzo, and the aryl group Ar is an aromatic ring group such as phenyl, naphthyl, anthracenyl, phenanthryl, pyridyl, thienyl, etc. n represents an integer with a carbon number of 0 or greater than 0, preferably an integer of 0 to 4, and n is more preferably 0 or 1.

[0013] Wherein, the above alkyl is preferably a C1-C10 alkyl, and the alkyl is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, heptyl, isopropyl, isobutyl, isopentyl, etc.; the above alkoxy is preferably a C1-C10 alkoxy, and the alkoxy is methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, etc.; the aryl Ar is preferably an aromatic ring group such as phenyl, naphthyl, anthracenyl, phenanthryl, etc.;

[0014] In the above-mentioned substituted phenyl or substituted biphenyl, the substitution can be mono-substitution or poly-substitution. In this case, the substituents in the substituted phenyl or substituted biphenyl are alkyl (specifically methyl, ethyl, propyl), alkoxy (specifically methoxy, ethoxy, propoxy, butoxy), halogen (specifically chlorine, bromine), nitro, phenyl, etc.

[0015] Furthermore, in formula (III) or (IV), R 1 It is one of hydrogen, fluorine, chlorine, bromine, allyl, nitro, cyano, trifluoromethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, phenyl, tolyl, trimethylphenyl, nitrophenyl, chlorophenyl, bromophenyl, biphenyl, methylbiphenyl, naphthyl, anthracenyl and phenanthryl, and the aryl group Ar is phenyl or naphthyl.

[0016] A method for preparing a cyclic phosphoric acid compound and its derivatives, which is a cyclic phosphoric acid compound containing a diaryl structural unit as shown in the above formula (III) or (IV), and the preparation method comprises the following steps:

[0017]

[0018] Step 1): Add compound (I), compound (II) and a solvent into a reactor, and after they are dissolved, add white phosphorus and a base in sequence, heat and stir to obtain a mixed solution of reactants.

[0019] Step 2): adding a base to the reaction mixture obtained in step 1) and heating to react. After the reaction is completed, stopping heating and cooling it to room temperature, adding an acid to the reactor for acidification reaction, thereby obtaining a compound of formula (III) or (IV).

[0020] In formula (II): R 2 It may be hydrogen, halogen, alkenyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, alkyl, alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted biphenyl, naphthyl, anthracenyl, phenanthryl, pyridyl, thienyl, benzoyl, or the like.

[0021] Among them, R 2 In the above, the alkyl group is preferably a C1-C10 alkyl group, and the alkyl group is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, heptyl, isopropyl, isobutyl, isopentyl, etc.; the alkoxy group is preferably a C1-C10 alkoxy group, and the alkoxy group is methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, etc.; the aromatic group Ar is preferably an aromatic ring group such as phenyl, naphthyl, anthracenyl, phenanthryl, etc.

[0022] Here, the substituted or unsubstituted phenyl group, the substituted or unsubstituted biphenyl group and the above R 1 The same definition as in .

[0023] The base used in step 1) is an alkali metal hydroxide, carbonate, phosphate or organic alcohol salt; an organic amine, and the base is preferably an organic amine (such as triethylamine, diethylamine, etc.) or an alkali metal hydroxide (such as sodium hydroxide, potassium hydroxide).

[0024] The solvent used in the reaction needs to contain dialkyl sulfoxide. Dialkyl sulfoxide can be used alone as a solvent, or other solvents can be used and mixed with dialkyl sulfoxide in a volume ratio of 100:1 to 0:1. Other solvents can be organic solvents that do not react with compounds (I), (II), white phosphorus and dimethyl sulfoxide, such as dimethyl sulfoxide (DMSO), acetonitrile (MeCN), tetrahydrofuran (THF), diethyl ether (Et2O), acetone, benzene, toluene, 1,4-dioxane, ethylene glycol dimethyl ether (DME) or tetramethylethylenediamine (TMEDA). The preferred solvent is dimethyl sulfoxide (DMSO) alone or a mixed solvent of dimethyl sulfoxide and other solvents. It is more preferred to use dimethyl sulfoxide (DMSO) alone.

[0025] In step 1), the heating temperature is in the range of 40°C to 120°C, and the reaction time is 2 to 8 hours. The preferred temperature range is 50 to 100°C, and the reaction time is 3 to 6 hours.

[0026] The molar ratio of the compound (I) and the compound (II) used in step 1) is 1.0 to 1.5 times and 0.2 to 2.0 times, respectively, relative to the phosphorus atom in white phosphorus (P4), and the molar ratio of the base used is 0.2 to 2.0 times relative to the phosphorus atom in white phosphorus (P4). The preferred ratio is that the compound (I) is 1.0 to 1.4 times the molar ratio of the phosphorus atom in white phosphorus, and the compound (II) is 0.4 to 0.9 times the molar ratio of the phosphorus atom in white phosphorus.

[0027] In step 2), when synthesizing compound (III), the base is an alkali metal hydroxide, an alkali metal carbonate, an alkali metal phosphate, an alkali metal organic alcohol salt or an organic amine, and the alkali metal is potassium or sodium, wherein potassium hydroxide is preferred. When synthesizing compound (IV), the base is sodium hydrosulfide, potassium hydrosulfide, sodium sulfide or ammonium sulfide, wherein sodium hydrosulfide is preferred.

[0028] The acid used in the acidification in step 2) is a strong inorganic acid, such as sulfuric acid (H2SO4), nitric acid (HNO3), hydrochloric acid (HCl), perchloric acid (HClO4), permanganic acid (HMnO4), hydroiodic acid (HI), hydrobromic acid (HBr), preferably hydrochloric acid (HCl) and hydrobromic acid (HBr).

[0029] In step 2), the heating temperature is from room temperature to 120° C., preferably from 60° C. to 80° C., and the reaction time is from 2 to 8 hours, preferably from 2 to 5 hours.

[0030] In step 2), the acidification reaction temperature is room temperature, and the reaction time is 0.5 to 4 hours, and the reaction time is preferably 1 to 3 hours.

[0031] The molar ratio of the base used in step 2) to the phosphorus atom in white phosphorus (P4) in step 1) is 1.0 to 2.5 times, preferably 1.5 to 2.0 times.

[0032] The amount of acid used in step 2) is controlled according to the pH, and the pH is acidified to 1-3.

[0033] Effects of the Invention

[0034] According to the present invention, a method for synthesizing cyclic phosphoric acid compounds and derivatives thereof from white phosphorus in one pot is provided. The conventional synthesis method requires multiple and complex reactions, for example, firstly reacting white phosphorus with chlorine to obtain a phosphorus trichloride intermediate, then reacting phosphorus trichloride with a biarylphenol substrate, and then obtaining cyclic phosphoric acid after acid hydrolysis. However, the method of the present invention does not require the use of phosphorus trichloride, thus avoiding the problem of using highly polluting chlorine and a large amount of acid in conventional phosphorus chemical production, and is a more environmentally friendly production method with simple reaction steps.

[0035] The cyclic phosphoric acid (e.g., phosphoric acid with a chiral binaphthyl diol skeleton) synthesized by the method of the present invention and its derivatives have very wide applications in the field of organic synthesis, especially in the field of asymmetric catalytic synthesis, and are a class of compounds of great value. Compared with the traditional synthesis route, the method disclosed by the present invention has mild reaction conditions, short reaction time, simple post-treatment, and can obtain a higher yield. DETAILED DESCRIPTION

[0036] The above invention contents of the present invention are further described in detail below through specific examples, but this should not be understood as any limitation on the scope of protection of the present invention. All technical solutions implemented based on the above contents of the present invention belong to the scope of the present invention. The present invention generally and / or specifically describes the materials and test methods used in the experiment. It is clear to those skilled in the art that, hereinafter, unless otherwise specified, the room temperature described in the present invention has a technical meaning known in the art, generally referring to 20 to 25°C; the chemicals described are all commercially available.

[0037] The present invention discloses a method for preparing a cyclic phosphate compound and a derivative thereof, which are a cyclic phosphate compound and a derivative thereof containing a diaryl structural unit and represented by formula (III) or (IV).

[0038]

[0039] Formula (III) or (IV): R 1 It can be hydrogen, halogen, alkenyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, alkyl with any carbon number, alkoxy with any carbon number, substituted or unsubstituted phenyl, substituted or unsubstituted biphenyl, naphthyl, anthracenyl, phenanthrenyl, pyridyl, thienyl, benzo, etc. The aryl Ar is an aromatic ring such as phenyl, naphthyl, anthracenyl, phenanthrenyl, pyridyl, thienyl, etc., and n represents an integer with a carbon number of 0 or greater than 0. n is preferably 0 or 1.

[0040] Here, the substituted or unsubstituted phenyl group and the substituted or unsubstituted biphenyl group have the same meanings as described above.

[0041] Preparation of compounds

[0042] A method for preparing a cyclic phosphate compound, the method comprising the following steps:

[0043]

[0044] Step 1): Add compound (I), compound (II) and a solvent into a reactor, dissolve them, then add white phosphorus and alkali in sequence, heat and stir to obtain a mixed solution of reactants.

[0045] Step 2): add a base to the reaction mixture obtained in step 1) and heat it for reaction. After the reaction is completed, stop heating and cool it to room temperature. Then add acid to the reactor for acidification reaction to obtain a compound of formula (III).

[0046] A method for preparing a derivative of a cyclic phosphate compound, the method comprising the following steps:

[0047]

[0048] Step 1): Add compound (I), compound (II) and a solvent into a reactor and dissolve them, then add white phosphorus and alkali in sequence, heat and stir to obtain a mixed solution of reactants.

[0049] Step 2): add a base to the reaction mixture obtained in step 1) and heat it for reaction. After the reaction is completed, stop heating and cool it to room temperature. Then add acid to the reactor for acidification reaction, thereby obtaining a compound of formula (IV).

[0050] In the above two reaction formulas, in the compound formula (I), R 1 It can be hydrogen, halogen, alkenyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, alkyl, alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted biphenyl, naphthyl, anthracenyl, phenanthryl, pyridyl, thienyl, etc. Aryl Ar is an aromatic ring group such as phenyl, naphthyl, anthracenyl, phenanthryl, pyridyl, thienyl, etc. n represents an integer with a carbon number of 0 or greater than 0;

[0051] In formula (II), X can be S, Se or Te, R 2 It may be hydrogen, halogen, nitro, cyano, trifluoromethyl, trifluoromethoxy, alkyl, alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted biphenyl, naphthyl, anthracenyl, phenanthrenyl, pyridyl, thienyl, etc.;

[0052] In formula (III) or (IV), R 1All of them can be hydrogen, halogen, nitro, cyano, trifluoromethyl, trifluoromethoxy, alkyl, alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted biphenyl, naphthyl, anthracenyl, phenanthryl, pyridyl, thienyl, benzo, etc. Aryl Ar is an aromatic ring group such as phenyl, naphthyl, anthracenyl, phenanthryl, pyridyl, thienyl, etc. n represents an integer of 0 or greater than 0 carbon number.

[0053] Here, the substituted or unsubstituted phenyl group, the substituted or unsubstituted biphenyl group and the above R 1 , R 2 The same definition as in .

[0054] The base used in step 1) of the above two reaction formulas is an alkali metal hydroxide, an alkali metal carbonate, an alkali metal phosphate, or an alkali metal organic alcohol salt or an organic amine, preferably an organic amine.

[0055] The solvent used in the above two reactions needs to contain dialkyl sulfoxide. Dialkyl sulfoxide can be used alone as the solvent, or other solvents can be used and mixed with dialkyl sulfoxide in a volume ratio of 100:1 to 0:1. Other solvents can be organic solvents that do not react with compounds (I), (II), white phosphorus and dimethyl sulfoxide, such as dimethyl sulfoxide (DMSO), acetonitrile (MeCN), tetrahydrofuran (THF), diethyl ether (Et2O), acetone, benzene, toluene, 1,4-dioxane, ethylene glycol dimethyl ether (DME) or tetramethylethylenediamine (TMEDA). The preferred solvent is dimethyl sulfoxide (DMSO) alone.

[0056] In step 1) of the above two reactions, the heating temperature is 40° C. to 120° C., and the reaction time is 2 to 8 hours.

[0057] The ratio of compound (I) and compound (II) used in step 1) of the above two reactions relative to white phosphorus (P4) is 1.0 to 1.5 times the molar equivalent and 0.2 to 2.0 times the molar equivalent, respectively, and the ratio of the base used relative to white phosphorus (P4) is 0.2 to 2.0 times the molar equivalent.

[0058] In step 2), the base used to synthesize compound (III) is an alkali metal hydroxide, carbonate, phosphate, organic alcohol salt or organic amine, and the alkali metal is potassium or sodium, wherein potassium hydroxide is preferred. The base used to synthesize compound (IV) is sodium hydrosulfide, potassium hydrosulfide, sodium sulfide or ammonium sulfide, wherein sodium hydrosulfide is preferred.

[0059] The acids used in the acidification described in step 2) of the above two reactions are all inorganic strong acids, such as sulfuric acid (H2SO4), nitric acid (HNO3), hydrochloric acid (HCl), perchloric acid (HClO4), permanganic acid (HMnO4), hydroiodic acid (HI), hydrobromic acid (HBr), preferably hydrochloric acid (HCl) and hydrobromic acid (HBr).

[0060] In step 2) of the above two reactions, the reaction temperature after adding the base is in the range of room temperature to 120°C, preferably 60 to 80°C, and the reaction is carried out at this temperature for 1 to 8 hours, preferably 2 to 5 hours.

[0061] In step 2) of the above two reactions, the reaction temperature of the acidification step is room temperature, and the reaction time is 0.5 to 4 hours, preferably 1 to 3 hours.

[0062] The molar ratio of the base used in step 2) of the above two reactions to the white phosphorus (P4) used in step 1) is 1.0 to 2.5 times, preferably 1.5 to 2.0 times.

[0063] The amount of acid used in step 2) of the above two reactions is controlled according to the pH, and is preferably acidified to a pH of 1-3.

[0064] The solvents used in the above steps 1) and 2) of the above two reactions may be the same or different. For ease of operation and post-treatment, it is preferred to directly carry out the operation of step 2) in the reaction solution of step 1) without purifying and separating the reaction product of step 1).

[0065] It can be seen from the above preparation method that in the preparation method disclosed in the present invention, the reaction conditions are very mild and the reaction time is also short. In addition, as can be seen from the reaction operation of the embodiments described below, the post-treatment operation is also simple and a higher yield can be obtained.

[0066] The preparation method of the above compounds is specifically described below through examples.

[0067] Synthesis of compounds of formula (III) or (IV)

[0068] Example 1: Synthesis of (S)-3,3'-dimethyl-1,1'-binaphthol phosphate

[0069]

[0070] In a glove box filled with nitrogen, (S)-3,3'-dimethyl-[1,1'-binaphthyl]-2,2'-diphenol (0.33mmol), diphenyl disulfide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10mL Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 80°C for 4 hours, KOH (0.6mmol) was added and alkaline hydrolysis was continued at 80°C for 3 hours. After the reaction was completed, dichloromethane and a 4M dilute hydrochloric acid solution were added, acidified to pH 3, and the organic phase was extracted several times. The combined organic phase was evaporated by rotary evaporation and the crude reaction mixture was purified by flash chromatography to obtain the product with a yield of 90% (yield calculated based on phosphorus atoms).

[0071] Main NMR data: 1 H NMR (500MHz, CD3OD): δ2.67(s,6H),7.13-7.18(m,4H),7.35-7.39(m,2H),7.83-7.85(m,4H); 13 C NMR (150MHz, CD3OD): δ18.0,123.4,125.9,126.2,127.7,128.7,130.8,132.0,132.7,149.7(d,J=9.5Hz); 31 P NMR (243MHz, CD3OD): δ2.4; HRMS calcd for[C 22 H 17 O4P]([M+H] + ):377.0938,found377.0937.

[0072] Example 2: Synthesis of (Rac)-binaphthyl diol phosphate

[0073]

[0074] In a glove box filled with nitrogen, (Rac)-binaphthol (0.36mmol), diphenyl disulfide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10mL Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 80°C for 3 hours, KOH (0.6mmol) was added and alkaline hydrolysis was continued at 80°C for 2 hours. After the reaction was completed, dichloromethane and a dilute hydrochloric acid solution with a concentration of 4M were added, acidified to a pH of about 2 and the organic phase was extracted multiple times. The combined organic phase was evaporated to dryness by a rotary evaporator and the crude reaction mixture was purified by flash chromatography to obtain the product in a 91% yield (yield calculation based on phosphorus atoms).

[0075] Main NMR data: 1 H NMR (600MHz, CD3OD): δ7.30-7.34(m,4H),7.50-7.53(m,2H),7.58(d,J=8.9Hz,2H),8.03(d,J=8.4Hz,2H),8.13(d,J=8.9Hz,2H); 13 C NMR (150MHz, CD3OD): δ121.8, 122.8, 126.7, 127.8, 129.7, 132.3, 133.1, 133.6, 148.8 (d, J = 9.7Hz); 31 PNMR (243MHz, CD3OD): δ3.7; HRMS calcd for[C 20 H 13 O4P]([M+H] + ):349.0625,found349.0628.

[0076] Example 3: Synthesis of (R)-3,3'-dimethoxy-1,1'-binaphthol phosphate

[0077]

[0078] In a glove box filled with nitrogen, (R)-3,3'-dimethoxy-[1,1'-binaphthyl]-2,2'-diphenol (0.33mmol), diphenyl diselenide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10mL Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 60°C for 5 hours, KOH (0.6mmol) was added and alkaline hydrolysis was continued at 70°C for 4 hours. After the reaction was completed, dichloromethane and a 4M dilute hydrochloric acid solution were added, acidified to pH 3 and the organic phase was extracted several times. The combined organic phase was evaporated by rotary evaporation and the crude reaction mixture was purified by flash chromatography to obtain the product with a yield of 82% (yield calculated based on phosphorus atoms).

[0079] Main NMR data: 1 H NMR (500MHz, CD3OD): δ4.03 (s, 6H), 7.03-7.13 (m, 4H), 7.35 (t, J = 7.5Hz, 2H), 7.53 (s, 2H), 7.84 (d, J = 8.3Hz, 2H); 13 C NMR (125MHz, CD3OD): δ56.6, 109.9, 124.2 (d, J = 2.7Hz), 125.3, 127.2, 127.7, 128.0, 128.5, 133.6, 140.3 (d, J = 9.2Hz), 151.6 (d, J = 2.7Hz); 31 P NMR (202MHz, CD3OD): δ3.5; HRMS calcd for[C 22 H 17 O6P]([M+H] + ):409.0836,found 409.0836.

[0080] Example 4: Synthesis of (R)-3,3'-diphenyl-1,1'-binaphthol phosphate

[0081]

[0082] In a glove box filled with nitrogen, (R)-3,3'-diphenyl-[1,1'-binaphthyl]-2,2'-diphenol (0.33mmol), diphenyl disulfide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10mL Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 80°C for 5 hours, KOH (0.6mmol) was added and alkaline hydrolysis was continued at 80°C for 3 hours. After the reaction was completed, dichloromethane and a 4M dilute hydrochloric acid solution were added, acidified to pH 1 and the organic phase was extracted several times. The combined organic phase was evaporated by rotary evaporation and the crude reaction mixture was purified by flash chromatography to obtain the product with a yield of 89% (yield calculated based on phosphorus atoms).

[0083] Main NMR data: 1 H NMR (600MHz, CD3OD): δ7.19-7.25(m,4H),7.31-7.33(m,2H),7.40(t,J=7.7Hz,4H) ,7.45(t,J=7.5Hz,2H),7.77(d,J=7.6Hz,4H),8.00(d,J=8.2Hz,2H),8.05(s,2H); 13 C NMR (150MHz, CD3OD): δ124.1,126.7,127.5,127.7,128.5,129.2,129.6,131.2,132.2,132.7,133.4,135.6,139.0,146.9(d,J=9.0Hz); 31 P NMR (243MHz, CD3OD): δ1.7; HRMS calcd for[C 32 H 21 O4P]([M+H] + ):501.1251, found 501.1253.

[0084] Example 5: Synthesis of (S)-3,3'-dibromo-1,1'-binaphthol phosphate

[0085]

[0086] In a glove box filled with nitrogen, (R)-3,3'-dibromo-[1,1'-binaphthyl]-2,2'-diphenol (0.33mmol), 4,4'-dichlorodiphenyl disulfide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10mL Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 80°C for 6 hours, KOH (0.6mmol) was added and alkaline hydrolysis was continued at 80°C for 2 hours. After the reaction was completed, dichloromethane and a 4M dilute hydrochloric acid solution were added, acidified to pH 2 and the organic phase was extracted several times. The combined organic phase was evaporated by rotary evaporation and the crude reaction mixture was purified by flash chromatography to obtain the product with a yield of 88% (yield calculated based on phosphorus atoms).

[0087] Main NMR data: 1 H NMR (500MHz, CD3OD): δ6.98(d,J=8.6Hz,2H),7.11(t,J=7.3Hz,2H),7.34(t,J=7.6Hz,2H),7.80(d,J=8.3Hz,2H),8.30(s,2H); 13 C NMR (125MHz, CD3OD): δ115.6 (d, J = 2.3Hz), 124.2, 127.5, 127.6, 128.2, 128.8, 132.4, 133.2, 135.0, 145.4 (d, J = 9.1Hz); 31 P NMR (202MHz, CD3OD): δ2.2; HRMS calcd for[C 20 H 11 Br2O4P]([M+H] + ):506.8814, found 506.8822.

[0088] Example 6: Synthesis of (R)-3,3'-bis(4-methoxyphenyl)-1,1'-binaphthol phosphate

[0089]

[0090] In a glove box filled with nitrogen, (R)-3,3'-bis(4-methoxyphenyl)-[1,1'-binaphthyl]-2,2'-diphenol (0.33mmol), 4,4'-difluorodiphenyl disulfide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10mL Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 80°C for 5 hours, KOH (0.6mmol) was added and alkaline hydrolysis was continued at 80°C for 4 hours. After the reaction was completed, dichloromethane and a 4M dilute hydrochloric acid solution were added, acidified to pH 3 and the organic phase was extracted several times. The combined organic phase was evaporated by rotary evaporation and the crude reaction mixture was purified by flash chromatography to obtain the product with a yield of 90% (yield calculated based on phosphorus atoms).

[0091] Main NMR data: 1 H NMR (600MHz, CDCl3): δ3.50 (s, 6H), 6.80 (d, J = 7.1Hz, 4H), 7.22-7.33 (m, 4H), 7.44-7.51 (m, 6H), 7.92 (t, J = 8.3Hz, 4H); 13 C NMR (150MHz, CDCl3): δ55.1,113.9,122.6,126.0,126.4,127.2,128.4,129.2,131.0,131.2,131.7,131.9,133.8,144.8(d,J=8.3Hz),159.3; 31 P NMR (243MHz, CDCl3): δ2.6; HRMS calcd for[C 34 H 25 O6P]([M+H] + ):561.1462, found 561.1463.

[0092] Example 7: Synthesis of (R)-3,3'-bis(4-nitrophenyl)-1,1'-binaphthol phosphate

[0093]

[0094] In a glove box filled with nitrogen, (R)-3,3'-bis(4-nitrophenyl)-[1,1'-binaphthyl]-2,2'-diphenol (0.33mmol), diphenyl disulfide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10mL Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 80°C for 6 hours, KOH (0.6mmol) was added and alkaline hydrolysis was continued at 80°C for 2 hours. After the reaction was completed, dichloromethane and a 4M dilute hydrochloric acid solution were added, acidified to pH 2 and the organic phase was extracted several times. The combined organic phase was evaporated by rotary evaporation and the crude reaction mixture was purified by flash chromatography to obtain the product with a yield of 84% (yield calculated based on phosphorus atoms).

[0095] Main NMR data: 1 H NMR (600MHz, CDCl3 / CD3OD=14:1): δ7.37(br,2H),7.55(br,1H),7.81(br,2H),8.00-8.03(m,2H),8.16(br,2H); 13 C NMR (150MHz, CDCl3 / CD3OD=14:1): δ122.9,123.3,126.4,127.0,127.4,128.6,130.8,131.2,131.6,131.8,132.5,143.8,144.3(d,J=7.2Hz),147.1; 31 P NMR (243MHz, CDCl3 / CD3OD=14:1): δ1.6; HRMS calcd for[C 32 H 19 N2O8P]([MH] + ):589.0806,found 589.0805.

[0096] Example 8: Synthesis of (R)-3,3'-bis(2,4,6-trimethylphenyl)-1,1'-binaphthol phosphate

[0097]

[0098] In a glove box filled with nitrogen, (R)-3,3'-bis(2,4,6-trimethylphenyl)-[1,1'-binaphthyl]-2,2'-diphenol (0.33mmol), 4,4'-dichlorodiphenyl disulfide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10mL Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 80°C for 6 hours, KOH (0.6mmol) was added and alkaline hydrolysis was continued at 60°C for 4 hours. After the reaction was completed, dichloromethane and a 4M dilute hydrochloric acid solution were added, acidified to pH 1 and the organic phase was extracted several times. The combined organic phases were evaporated to dryness on a rotary evaporator and the crude reaction mixture was purified by flash chromatography to give the product in 90% yield (yield calculated based on phosphorus atoms).

[0099] Main NMR data: 1 H NMR (500MHz, CDCl3): δ1.90(s,6H),2.00(s,6H),2.06(s,6H),6.60(s,2H),6.75(s ,2H),7.22-7.33(m,4H),7.42(t,J=7.4Hz,2H),7.65(s,2H),7.87(d,J=8.0Hz,2H); 13 C NMR (125MHz, CDCl3): δ20.4,21.0,21.3,122.8,125.2,126.1,127.2,127.5,128.1,1 28.2,131.1,131.2,132.5,133.1,134.8,137.1,137.6,137.9,146.9(d,J=10.0Hz); 31 P NMR (202MHz, CDCl3): δ4.3; HRMS calcd for[C 38 H 33 O4P]([MH] + ):583.2043,found 583.2035.

[0100] Example 9: Synthesis of (S)-6,6'-dibromo-1,1'-binaphthol phosphate

[0101]

[0102] In a glove box filled with nitrogen, (S)-6,6'-dibromo-[1,1'-binaphthyl]-2,2'-diphenol (0.33mmol), 4,4'-dibromodiphenyl disulfide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10mL Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 80°C for 6 hours, KOH (0.6mmol) was added and alkaline hydrolysis was continued at 80°C for 2 hours. After the reaction was completed, dichloromethane and a 4M dilute hydrochloric acid solution were added, acidified to pH 3 and the organic phase was extracted several times. The combined organic phase was evaporated by rotary evaporation and the crude reaction mixture was purified by flash chromatography to obtain the product with a yield of 83% (yield calculated based on phosphorus atoms).

[0103] Main NMR data: 1 H NMR (500MHz, DMSO-d6): δ7.14(d,J=9.0Hz,2H),7.50(dd,J=9.3Hz,J=2.0Hz,2H),7.55(d,J=9.0Hz,2H),8.12(d,J=8.8Hz,2H),8.36(d,J=1.8Hz,2H); 13 C NMR (125MHz, DMSO-d6): δ118.2, 121.2, 123.2, 128.1, 129.6, 129.9, 130.3, 132.0, 149.2 (d, J = 9.5Hz); 31 P NMR (202MHz, DMSO-d6): δ3.0; HRMS calcd for[C 20 H 11 Br2O4P]([MH] + ):504.8668, found 504.8670.

[0104] Example 10: Synthesis of (R)-VANOL Phosphoric Acid

[0105]

[0106] In a glove box filled with nitrogen, (2R)-3,3'-diphenyl[2,2'-binaphthyl]-1,1'-diol (0.33mmol), diphenyl disulfide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10mL Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 80°C for 5 hours, KOH (0.6mmol) was added and alkaline hydrolysis was continued at 80°C for 3 hours. After the reaction was completed, dichloromethane and a 4M dilute hydrochloric acid solution were added, acidified to pH 1.5 and the organic phase was extracted several times. The combined organic phase was evaporated by rotary evaporation and the crude reaction mixture was purified by flash chromatography to obtain the product with a yield of 83% (yield calculated based on phosphorus atoms).

[0107] Main NMR data: 1 H NMR (600MHz, CD3OD): δ6.48(d,J=7.6Hz,4H),6.92(t,J=7.5Hz,4H),7.10(t,J=7.3Hz,2H),7.51( s,2H),7.59(t,J=7.3Hz,2H),7.65(t,J=7.9Hz,2H),7.88(d,J=8.1Hz,2H),8.47(d,J=8.1Hz,2H); 13 C NMR (150MHz, CD3OD): δ123.7, 124.3 (d, J = 2.1Hz), 127.2 (d, J = 2.2Hz), 127.3, 127 .7,127.9,128.6,128.8,128.9,130.1,135.7,141.4,141.5,147.7(d,J=9.8Hz); 31 P NMR (243MHz, CD3OD): δ3.2; HRMS calcd for[C 32 H 21 O4P]([MH] + ):499.1104,found499.1106.

[0108] Example 11: Synthesis of 2,2'-biphenyldiphenol phosphoric acid

[0109]

[0110] In a glove box filled with nitrogen, 2,2'-biphenyldiphenol (0.36mmol), diphenyl disulfide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10mL Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 60°C for 6 hours, KOH (0.6mmol) was added and alkaline hydrolysis was continued at 80°C for 3 hours. After the reaction was completed, dichloromethane and a 4M dilute hydrochloric acid solution were added, acidified to a pH of about 2 and the organic phase was extracted several times. The combined organic phase was evaporated by rotary evaporation and the crude reaction mixture was purified by flash chromatography to obtain the product with a yield of 89% (yield calculated based on phosphorus atoms).

[0111] Main NMR data: 1 H NMR (600MHz, CD3OD): δ7.29 (d, J = 8.0Hz, 2H), 7.39 (t, J = 7.5Hz, 2H), 7.48 (d, J = 7.5Hz, 2H), 7.60-7.61 (m, 2H); 13 C NMR (150MHz, CD3OD): δ122.5 (d, J = 4.4Hz), 127.3, 130.1, 130.9, 131.1, 149.8 (d, J = 9.1Hz); 31 P NMR (243MHz, CD3OD): δ2.5; HRMS calcd for[C 12 H9O4P]([MH] + ):247.0165,found 247.0165.

[0112] Example 12: Synthesis of 5,5'-diallyl-2,2'-biphenyl diphenol phosphoric acid

[0113]

[0114] In a glove box filled with nitrogen, 5,5'-diallyl-2,2'-biphenyldiphenol (0.36mmol), diphenyl disulfide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10mL Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 80°C for 4 hours, KOH (0.6mmol) was added and alkaline hydrolysis was continued at 80°C for 3 hours. After the reaction was completed, dichloromethane and a 4M dilute hydrochloric acid solution were added, acidified to pH 1 and the organic phase was extracted several times. The combined organic phase was evaporated by rotary evaporation and the crude reaction mixture was purified by flash chromatography to obtain the product with a yield of 83% (yield calculated based on phosphorus atoms).

[0115] Main NMR data: 1 H NMR (600MHz, CD3OD): δ3.47 (d, J = 4.9Hz, 4H), 5.08-5.14 (m, 4H), 5.98-6.04 (m, 2H), 7.20-7.39 (m, 6H); 13 C NMR (150MHz, CD3OD): δ40.4, 116.5, 122.3 (d, J = 3.3Hz), 129.8, 130.8, 131.2, 138.5, 139.8, 147.9 (d, J = 9.7Hz); 31 P NMR (243MHz, CD3OD): δ2.6; HRMS calcd for[C 18 H 17 O4P]([MH] + ):327.0791,found 327.0791.

[0116] Example 13: Synthesis of 3,3',5,5'-tetramethyl-2,2'-biphenyl diphenol phosphate

[0117]

[0118] In a glove box filled with nitrogen, 3,3',5,5'-tetramethyl-2,2'-biphenyldiphenol (0.33mmol), diphenyl disulfide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10ml Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 80°C for 4 hours, KOH (0.6mmol) was added and alkaline hydrolysis was continued at 80°C for 3 hours. After the reaction was completed, dichloromethane and a 4M dilute hydrochloric acid solution were added, acidified to pH 3 and the organic phase was extracted several times. The combined organic phase was evaporated by rotary evaporation and the crude reaction mixture was purified by flash chromatography to obtain the product with a yield of 88% (yield calculated based on phosphorus atoms).

[0119] Main NMR data: 1 H NMR (600MHz, CD3OD): δ2.36(s,6H),2.37(s,6H),7.14(s,2H),7.16(s,2H); 13 C NMR (150MHz, CD3OD): δ16.5, 20.9, 128.9, 130.0, 131.2 (d, J = 3.8Hz), 132.7, 136.7, 145.9 (d, J = 9.5Hz); 31 P NMR (243MHz, CD3OD): δ3.0; HRMS calcd for[C 16 H 17 O4P]([MH] + ):303.0791, found 303.0793.

[0120] Example 14: Synthesis of (S)-3,3'-dimethyl-1,1'-binaphthol thiophosphoric acid

[0121]

[0122] In a glove box filled with nitrogen, (S)-3,3'-dimethyl-[1,1'-binaphthyl]-2,2'-diphenol (0.33mmol), diphenyl disulfide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10mL Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 80℃ for 4 hours, NaSH (0.6mmol) was added and the reaction was continued at 80℃ for 3 hours. After the reaction was completed, dichloromethane and a 4M dilute hydrochloric acid solution were added, acidified to pH 3, and the organic phase was extracted several times. The combined organic phase was evaporated by rotary evaporation and the crude reaction mixture was purified by flash chromatography to obtain the product with a yield of 90% (yield calculated based on phosphorus atoms).

[0123] Main NMR data: 1 H NMR (500MHz, CDCl3): δ2.42(s,3H),2.54(s,3H),7.06-7.16(m,4H),7.28-7.36 (m,2H),7.46(s,1H),7.62(d,J=8.2Hz,1H),7.72(s,1H),7.77(d,J=8.4Hz,1H); 13 C NMR (125MHz, CDCl3): δ17.8,18.4,122.3,122.7,125.37,125.43,125.51,125.68,126.8,127.0,127.7, 129.8,130.3,130.57,130.60,131.11,131.16,131.4,131.6,147.3(d,J=9.7Hz),147.8(d,J=12.7Hz); 31 P NMR (202 MHz, CDCl3): δ 65.0.

[0124] Example 15: Synthesis of (R)-3,3'-diphenyl-1,1'-binaphthol phosphate

[0125]

[0126] In a glove box filled with nitrogen, (R)-3,3'-diphenyl-[1,1'-binaphthyl]-2,2'-diphenol (0.33mmol), diphenyl disulfide (80mol%, 0.24mmol) and DMSO (3mL) were placed in a 10mL Schlenk tube with a stirrer. Then white phosphorus-toluene solution (9.3mg P4, 0.3mmol P-atom, dissolved in 320μL toluene) and Et3N (0.06mmol) were added in sequence. After the reaction mixture was stirred at 80°C for 5 hours, NaSH (0.6mmol) was added and alkaline hydrolysis was continued at 80°C for 3 hours. After the reaction was completed, dichloromethane and a 4M dilute hydrochloric acid solution were added, acidified to pH 1 and the organic phase was extracted several times. The combined organic phase was evaporated by rotary evaporation and the crude reaction mixture was purified by flash chromatography to obtain the product with a yield of 89% (yield calculated based on phosphorus atoms).

[0127] Main NMR data: 1 H NMR (500MHz, CDCl3): δ7.11-7.52(m,14H),7.63(d,J=7.7Hz,2H),7.85(s,1H),7.91(d,J=8.3Hz,2H),7.98(s,1H),8.01(d,J=8.3Hz,2H); 13 C NMR (125MHz, CDCl3): δ123.6,123.9,125.7,125.9,126.3 126.6,127.1,127.3,127.8,128.3,128.4,128.5,129.8,130.4,130.7,131.1,131.2,131 .5,132.37,132.41,133.9,134.8,137.9,138.5,145.5(d,J=9.3Hz),146.0(d,J=13.7Hz); 31 P NMR (202 MHz, CDCl3): δ 62.6.

[0128] Availability of industry

[0129] The cyclic phosphoric acid compounds containing diaryl structural units and derivatives thereof of the present invention are widely used as organic phosphorus ligands in asymmetric catalysis.

Claims

1. A method for preparing a cyclic phosphoric acid compound and a derivative thereof, which is a method for preparing a cyclic phosphoric acid compound containing a diaryl structural unit and a derivative thereof represented by the following formula (III) or (IV), In formula (III) or (IV), R 1 is one of hydrogen, halogen, alkenyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, alkyl, alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted biphenyl, naphthyl, anthracenyl, phenanthryl, pyridyl, thienyl or benzo; aryl Ar is phenyl, naphthyl, anthracenyl, phenanthryl, pyridyl or thienyl; n represents an integer having a carbon number of 0 or greater; X is oxygen or sulfur; The preparation method comprises the following steps: Step 1): firstly add compound (I), compound (II) and solvent into a reactor, then add white phosphorus and alkali in sequence, heat and stir to obtain a mixed solution of reactants, Step 2): adding a base to the mixed solution of the reactants obtained in step 1) and heating to react, stopping heating after the reaction is completed and cooling to room temperature, and then adding an acid to the reactor for acidification reaction, thereby obtaining a compound of formula (III) or (IV), Here, in formula (I) and formula (II), R 1 , R 2 are respectively one of hydrogen, halogen, alkenyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, alkyl, alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted biphenyl, naphthyl, anthracenyl, phenanthryl, pyridyl or thienyl, the aryl group Ar is phenyl, naphthyl, anthracenyl, phenanthryl, pyridyl or thienyl, n in formula (I) represents an integer having a carbon number of 0 or greater than 0; X in formula (II) is S, Se or Te.

2. The preparation method according to claim 1, wherein The base used in step 1) is an alkali metal hydroxide, carbonate, phosphate, organic alcohol salt; or an organic amine.

3. The preparation method according to claim 1, wherein In step 1), the heating temperature is 40° C. to 120° C., and the reaction time is 2 to 8 hours.

4. The preparation method according to claim 1, wherein The molar ratio of compound (I) and compound (II) used in step 1) is 1.0 to 1.5 times and 0.2 to 2.0 times, respectively, relative to the phosphorus atoms in white phosphorus, and the molar ratio of the base used is 0.2 to 2.0 times, relative to the phosphorus atoms in white phosphorus.

5. The preparation method according to claim 1, wherein In step 2), the base used to synthesize compound (III) is an alkali metal hydroxide, carbonate, phosphate, organic alcohol salt or organic amine, and the base used to synthesize compound (IV) is sodium hydrosulfide, potassium hydrosulfide, sodium sulfide or ammonium sulfide.

6. The preparation method according to claim 1, wherein The acid used in the acidification in step 2) is a strong inorganic acid, and the pH is acidified to 1-3.

7. The preparation method according to claim 1, wherein In step 2), the reaction temperature after adding the base is room temperature to 120° C., and the reaction time is 1 to 8 hours.

8. The preparation method according to claim 1, wherein The molar ratio of the base used in step 2) to the phosphorus atom in white phosphorus used in step 1) is 1.0 to 2.5 times the molar equivalent.

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