CN115246765A

CN115246765A - Preparation method and application of spirocyclic diphenol and diphosphonite thereof

Info

Publication number: CN115246765A
Application number: CN202110464585.2A
Authority: CN
Inventors: 张润通; 彭江华
Original assignee: Huizhou Kailisi Technology Co ltd
Current assignee: Huizhou Kailisi Technology Co ltd
Priority date: 2021-04-26
Filing date: 2021-04-26
Publication date: 2022-10-28
Anticipated expiration: 2041-04-26

Abstract

The invention discloses two spirocyclic diphenol frameworks: namely: 4,4', 6' -tetra-tert-butyl-1, 1 '-spiroindane-7, 7' -diol and 4,4 '-dimethoxy-6, 6' -di-tert-butyl-1, 1 '-spiroindane-7, 7' -diol and phosphonite compounds thereof. The method takes 3-hydroxybenzaldehyde or 5-hydroxy-2-methoxybenzaldehyde as starting materials, and only four steps of reaction are used, namely: alkylation, aldol condensation, hydrogenation reduction, cyclodehydration to obtain corresponding racemic spirodiphenol, and esterification of spirodiphenol to obtain spirocyclic diphosphonite compound. The method has the advantages of short synthesis steps, 70% of four-step yield of the spirodiphenol, simple post-treatment, no need of using precious metal palladium carbon, good economy and suitability for mass production. The spiro bisphosphinite has a structure shown in a general formula I, and a ligand formed by the spiro bisphosphinite and a transition metal shows excellent reaction activity, selectivity and stability in an olefin hydroformylation reaction. Meanwhile, the invention discloses a hydroformylation reaction of rhodium/spiro diphosphonite ligand by using cheap ether-carbon four or MTO-carbon four as raw materials to prepare valeraldehyde.

Description

Preparation method and application of spiro diphenol and diphosphonite thereof

Technical Field

The invention relates to a preparation method and application of spiro-diphenol skeleton 4,4', 6' -tetra-tert-butyl-1, 1 '-spiroindane-7, 7' -diphenol and 4,4 '-dimethoxy-6, 6' -di-tert-butyl-1, 1 '-spiroindane-7, 7' -diphenol and diphosphonite compounds thereof.

Background

The axisymmetric organic compound is always a research hotspot in the field of asymmetric catalysis, and the axisymmetric compound has wide application in the fields of biomedicine, industrial catalysis, functional materials and the like. Biaryl ligands such as BINOL and BINAP which have been successfully commercialized recently have been widely used.

In 1999, birman et al obtained racemic spiroindandiol ((. + -.) -SPINOL from acetone and 3-methoxybenzaldehyde via a six-step reaction. The diastereomers of the diphenols and menthyl chloroformate may be separated by column chromatography to provide optically pure (R) - (+) -SPINOL and (S) - (-) -SPINOL. Similar synthetic routes and resolution methods are also reported in US20130135574A1, CN 1055003542A. On the basis, zhongchinlin of the university of Nankai reported more practical resolution methods in 2002, and the methods utilize the characteristic that benzyl cinchonidine chloride and one of enantiomers easily form an inclusion compound, and can obtain optically pure spiroindane diphenol through simple steps of refluxing, cooling, crystallizing, filtering, acidifying and the like. 2016, bin et al reported the asymmetric synthesis of SPINOL catalyzed by chiral phosphonic acid directly from the one-step cyclodehydration of 1, 5-bis (5-hydroxy-2-methylphenyl) -3-pentanone to (S) -4,4' -dimethyl-7, 7' -dihydroxy-1, 1' -spiroindane (97% yield, 90% ee). It is worth mentioning that the ligands used by them are phosphonic acids with a chiral SPINOL backbone. In addition, CN109761774A studied a method from Friedel-crafts cyclization of 1, 5-bis (3-hydroxyphenyl) -3-pentanone to racemic SPINOL, which is the first report that the synthesis of 1,1 '-spiroindane-7, 7' -diphenol can be performed by cyclization without occupying group at hydroxyl para position.

Hydroformylation has found a very large industrial application since its discovery in 1938 by professor Otto Roelen. The production and consumption of butyraldehyde by hydroformylation of propylene as a raw material and production of butanol and octanol (mainly used for producing dioctyl phthalate (DOP)) by condensation hydrogenation are the largest, and the domestic annual demand is over 300 million tons. Because DOP is small and volatile in molecular weight, the global trend is to use higher molecular weight, low volatility and more stable plasticizers based on environmental and health safety considerations. And 2-propyl heptanol (2-PH) is prepared by performing condensation hydrogenation on valeraldehyde produced by butene hydroformylation, and the DPHP plasticizer produced from 2-PH can well solve the worry of DOP in the aspects of environmental protection, health and safety. To date, the united states and countries of the european union have begun to replace DOP with DPHP, a trend that has begun to impact asian markets.

The mixed carbon four hydroformylation method is the most economical and direct route which is generally accepted in the production process of valeraldehyde reported at present. A catalytic system consisting of biphenyl diphosphonite type ligands (Biphephos) and rhodium developed by United states carbonization (Toho chemical) can effectively carry out hydroformylation reaction on 2-butene in mixed C4 and can obtain high normal-iso ratio. Bisphosphinite ligands such as those proposed in US4668651, US4769498, US4148830, CN86106770 and CN86106811 can bring their positive to positive anisotropy to 26. Whereas the fourth generation bisphosphonite catalyzed hydroformylation production process based on Biphephos has been industrialized.

Bidentate and multidentate phosphonite/phosphoramidite ligands with biphenyl, binaphthyl and anthracene skeletons (e.g. Biphephos, anthraneetriol-based triphosphates) are widely reported and patented by foreign large chemical companies such as basf, dow chemical and winning and some research groups, while spiro bisphosphinite/phosphoramidite ligands are very rarely reported in hydroformylation reactions. In 2012, buiquin et al reported that a series of spiroketal bis-phosphoramidite ligands showed excellent conversion (90%) and normal to iso ratio (l/b = 174.4) in hydroformylation of 1-hexene and other terminal alkenes, but conversion in the hydroformylation of catalytic internal olefins (e.g., trans-2-butene) was only less than 15%. Therefore, the development of novel spiro diphosphine ligands with higher efficiency, selectivity and stability has important significance and industrial application value.

The novel preparation method of the spirocyclic diphenol and the diphosphonite ligand thereof, which is developed by the invention, has the characteristics of easy synthesis, suitability for large-scale synthesis, no expensive reagent and metal catalyst, industrialization and the like, and only four-step reaction is carried out from the initial raw material to the racemic spirocyclic diphenol. The process has the characteristics of simple route, 70 percent of four-step yield, avoidance of violent and dangerous experimental conditions and reagents, recycling of raw materials and the like. In addition, the novel spiro diphosphonite ligand (racemate) can be used for catalyzing hydroformylation reaction by using cheap ether carbon four or MTO carbon four as raw materials.

Disclosure of Invention

The embodiment of the invention aims to provide a preparation method and application of spirocyclic diphenol and diphosphonite thereof.

The embodiment of the invention is realized by that the spirocyclic diphenol and diphosphonite compound thereof have the structure shown in the general formula I:

wherein, the structure of the general formula I and the derivative thereof is shown as follows:

another objective of the embodiments of the present invention is to provide a preparation method and an application of a spiro-diphenol and a diphosphonite compound thereof, where the spiro-diphosphonite compound is formed by using 4,4', 6' -tetra-tert-butyl-1, 1 '-spiroindane-7, 7' -diphenol compound or 4,4 '-dimethoxy-6, 6' -di-tert-butyl-1, 1 '-spiroindane-7, 7' -diphenol as a raw material, and reacting the raw material with chlorophosphite containing an aryl or cyclic aryl structure under the action of an organic solvent and n-butyl lithium or triethylamine; the spiro diphosphonite ligand is one of L1-L31.

Drawings

FIG. 1 is a small batch olefin test evaluation apparatus used in comparative examples of the present invention.

Detailed Description

The present invention will be described in detail with reference to the accompanying drawings and examples, so that the objects, technical solutions and advantages of the present invention will be more clearly understood. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

The invention discloses a synthetic route of two spirodiphenol frameworks, which is characterized in that 3-hydroxybenzaldehyde or 5-hydroxy-2-methoxybenzaldehyde is used as a starting material, corresponding spirodiphenol is obtained after alkylation, aldol condensation, hydrogenation reduction and cyclodehydration, and then the spirodiphenol and chlorophosphinite are subjected to esterification reaction to obtain a spirocyclic diphosphonite ligand.

Specifically, the synthesis method of the present invention is specifically described as follows:

in some embodiments, 3-hydroxybenzaldehyde or 5-hydroxy-2-methoxybenzaldehyde is alkylated with isobutylene under lewis acid catalysis to give 2, 4-di-tert-butyl-5-hydroxybenzaldehyde (2) or 2-methoxy-4-tert-butyl-5-hydroxybenzaldehyde (2 a).

In some embodiments, the protic or lewis acid used in the alkylation reaction is one or more of an organic acid or an inorganic acid, such as: formic acid, acetic acid, oxalic acid, dichloroacetic acid, trifluoroacetic acid, propionic acid, malonic acid, pyruvic acid, butyric acid, valeric acid, caproic acid, adipic acid, benzoic acid, p-nitrobenzoic acid, terephthalic acid, benzenesulfonic acid, fluorosulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, and the like; inorganic acids such as: hydrobromic acid, hydrochloric acid, hydrofluoric acid, sulfurous acid, sulfuric acid, perchloric acid, phosphonic acid, pyrophosphoric acid, nitric acid, nitrous acid, chromic acid, fluoroantimonic acid, and the like; the alkylating reagent is any one of bromo-tert-butane, chloro-tert-butane, isobutene and tert-butanol; the reaction temperature is 80-140 ℃, and the reaction solvent is any one of benzene, toluene, p-xylene, o-xylene, chlorobenzene or dichlorobenzene.

In some embodiments, intermediate 2 or 2a is aldolized with acetone to yield 1, 5-bis (2, 4-di-tert-butyl-5-hydroxyphenyl) -1, 4-pentadien-3-one (3) or 1, 5-bis (2-methoxy-4-tert-butyl-5-hydroxyphenyl) -1, 4-pentadien-3-one (3 a).

In some embodiments, the condensation reaction of intermediate 2 or 2a with acetone is carried out in a solvent after mixing in the presence of a base.

In some more preferred embodiments, the base is any one of potassium hydroxide, sodium hydroxide, potassium carbonate, sodium tert-butoxide, potassium tert-butoxide; the dosage of the alkali is 1.5 to 10 equivalents, the solvent is ethanol, water or a mixed solvent thereof, the proportion of the mixed solvent is between 50 and 90, and the reaction temperature is 20 to 75 ℃.

In some embodiments, intermediate 3 or 3a is subjected to hydrogenation reduction of a carbon-carbon double bond under catalysis of a metal catalyst to obtain 1, 5-bis (2, 4-di-tert-butyl-5-hydroxyphenyl) -3-pentanone (4) or 1, 5-bis (2-methoxy-4-tert-butyl-5-hydroxyphenyl) -3-pentanone (4 a).

In some embodiments, the catalyst for the reduction reaction is any one of raney nickel, ferric chloride, cobalt oxide, or palladium on carbon; the dosage of the reduction catalyst is 1-20% (w/w), the hydrogen pressure is 0.05-5 MPa, the reaction temperature is 20-50 ℃, and the reaction time is 24-72 hours. The reaction solvent is any one of ethyl acetate, tetrahydrofuran, dichloromethane or 1, 4-dioxane.

In some embodiments, intermediate 4 or 4a is cyclized under the action of a dehydrating agent to give 4,4',6,6' -tetra-tert-butyl-1, 1 '-spiroindane-7, 7' -diol (5) or 4,4 '-dimethoxy-6, 6' -di-tert-butyl-1, 1 '-spiroindane-7, 7' -diol (5 a).

In some embodiments, the dehydrating agent is any one of polyphosphoric acid, concentrated sulfuric acid, acetic anhydride, methanesulfonic acid, benzoic acid, p-toluenesulfonic acid, anhydrous aluminum trichloride. The reaction solvent is any one of toluene, n-heptane, dichloromethane, trichloromethane and dichloroethane. The dosage of the dehydrating agent is 10 to 70 equivalent, the reaction temperature is 45 to 135 ℃, and the reaction time is 2 to 6 hours.

In some embodiments, intermediate 5 or 5a is reacted with n-butyllithium to provide a lithiated reaction solution; and reacting the reaction liquid after lithiation with chlorophosphinite containing aryl or cyclic aryl structure to obtain the spiro diphosphonite compound with large steric hindrance.

In some embodiments, intermediate 5 or 5a is reacted with a mixed solution of chlorophosphinite containing aryl or cyclic aryl structure and an acid-binding agent to obtain the large sterically hindered spiro bisphosphinite compound.

In some embodiments, n-butyllithium is used in an amount of 2 to 4 equivalents in the esterification reaction; the acid binding agent is any one of triethylamine, N-diisopropylethylamine and pyridine, and the dosage is 5-20 equivalent; the reaction temperature is-78-80 ℃, the reaction time is 12-48 hours, and the reaction solvent is any one of toluene, tetrahydrofuran, diethyl ether, 2-methyl tetrahydrofuran, methyl tert-butyl ether, isopropyl ether, anisole, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, butyl ether, cyclopentyl methyl ether or 1, 4-dioxane.

Example 1: preparation of 2, 4-di-tert-butyl-5-hydroxybenzaldehyde (2)

1 (20.0 g,163.8 mmol) was charged into a 2L double-necked flask, the reaction flask was replaced with a nitrogen atmosphere, and 200ml of tetrahydrofuran and concentrated sulfuric acid (2.5 g) were added thereto at 25 ℃. Isobutene under 1.5 atmospheres is continuously introduced, and the reaction is continued for 12 hours by heating to 100 ℃. After the reaction solution was quenched with water, 300ml of water was added and extracted three times with ethyl acetate (300 ml each). The organic phase obtained was dried over anhydrous sodium sulfate and then spin-dried under reduced pressure to give 35.7g of a pale yellow solid with a yield of 94%. ¹ H NMR(400MHz,CDCl ₃ ):δ＝1.35(s,9H),1.41 (s,9H),6.54(s,1H),7.30(d,1H),7.38(s,1H),9.89(d,1H)。

Example 2: 2-methoxy-4-tert-butyl-5-hydroxybenzaldehyde (2 a)

The procedure for the synthesis of intermediate 2a was similar to that of intermediate 2, with 20g of intermediate 1a being dosed to give 26.3g of a yellow solid with 96% yield. ¹ H NMR(400MHz,CDCl ₃ ):δ＝1.39(s,9H),3.89(s,3H), 6.62(s,1H),6.96(s,1H),7.36(d,1H)。

Example 3:1, 5-bis (2, 4-di-tert-butyl-5-hydroxyphenyl) -1, 4-pentadien-3-one (3)

A500 ml two-necked flask was charged with 1 (20.0g, 85.3mmol), acetone (3.1ml, 42.7mmol) and125ml of ethanol and a mixed solution is formed. Subsequently, the mixed solution was transferred to a 200ml dropping funnel, and 400ml of an aqueous ethanol solution of sodium hydroxide (19.0 g of NaOH, etOH-H) was slowly dropped ₂ O, 65%). After the dropwise addition, the mixture was stirred at room temperature for 2 hours, and the organic phase was diluted with dichloromethane, washed with water, dried over anhydrous sodium sulfate, and separated by flash column chromatography to give 19.3g of the target product as a pale yellow oil, which was then allowed to stand for solidification in a yield of 92%. ¹ H NMR(400MHz,CDCl ₃ ):δ＝1.31(s,18H),1.38(s,18H),6.60(s,2H), 6.70–6.83(m,4H),7.35(s,2H),7.75(d,2H)。

Example 4:1, 5-bis (2-methoxy-4-tert-butyl-5-hydroxyphenyl) -1, 4-pentadien-3-one (3 a)

The synthesis procedure of intermediate 3a is similar to that of intermediate 3, and 20g of intermediate 2a is fed, so that 19.6g of target product in yellow oil is finally obtained with the yield of 95%. ¹ H NMR(400MHz,CDCl ₃ ):δ＝1.43(s,18H),3.88 (s,6H),6.69–7.01(m,8H),7.82(d,2H)。

Example 5:1, 5-bis (2, 4-di-tert-butyl-5-hydroxyphenyl) -3-pentanone (4)

In a 500ml round-bottomed flask, 3 (15.0 g,30.6 mmol), 200ml of acetone and 60g of Raney nickel were added in this order. Then, a hydrogen balloon was inserted and the reaction was stirred under hydrogen atmosphere, and the progress of the reaction was monitored by TLC. When the starting point had disappeared (reaction time: about 1 day), the catalyst was filtered off, washed with acetone and the filtrate was dried under reduced pressure to give the desired product in the form of a colorless oil 14.97g with a yield of 99%. ¹ H NMR(400MHz,CDCl ₃ ):δ＝1.36(d,36H), 2.71–3.03(m,8H),6.07(s,2H),6.54(t,2H),7.15(s,2H)。

Example 6:1, 5-bis (2-methoxy-4-tert-butyl-5-hydroxyphenyl) -3-pentanone (4 a)

The synthesis procedure of intermediate 4a is similar to that of intermediate 4, and intermediate 3a is charged with 15g, so that 14.7g of the target product is finally obtained as yellow oil with the yield of 97%. ¹ H NMR(400MHz,CDCl ₃ ):δ＝1.43(s,18H),2.75 –2.91(m,8H),3.73(s,6H),6.03(s,2H),6.42(t,2H),6.77(s,2H)。

Example 7:4,4', 6' -tetra-tert-butyl-1, 1 '-spiroindane-7, 7' -diol (5)

In a 500ml round bottom flask, 4 (11.0 g, 22.2mmol), 105g of polyphosphoric acid were added in this order, and the mixture was heated and stirred at 120 ℃ for 6 hours. After the reaction is finished, washing with water, extracting an organic phase with ethyl acetate, drying with anhydrous sodium sulfate, performing rotary drying under reduced pressure to obtain a crude product, and separating by flash column chromatography. Recrystallization from n-hexane gave 22.8g of the target product in 78% yield. ¹ H NMR(400MHz,CDCl ₃ ):δ＝1.37 (d,36H),2.31(m,4H),3.04–3.27(m,4H),5.44(s,2H),7.09(s,2H)。

Example 8:4,4 '-dimethoxy-6, 6' -di-tert-butyl-1, 1 '-spiroindane-7, 7' -diol (5 a)

The synthesis procedure of the intermediate 5a is similar to that of the intermediate 5, and 11.0g of the intermediate 4a is fed, so that 14.7g of the target product is finally obtained, and the yield is 81%. ¹ H NMR(400MHz,CDCl ₃ ):δ＝1.44(s,18H),2.52–2.18 (m,4H),2.91–3.11(m,4H),3.79(s,6H),5.25(s,2H),6.66(s,2H)。

Example 9: preparation of 7,7 '-bis [ (1, 1' -biphenyl-2, 2 '-diyl) phosphonite ] -4,4',6 '-tetra-tert-butyl-1, 1' -spiroindane (6-L4)

5 (5.0 g,10.5 mmol), anhydrous triethylamine (21.9ml, 157.5mmol, 15eq.) and 80ml of anhydrous tetrahydrofuran were added in this order under nitrogen protection in a dry 500ml Schlenk flask. Then, after cooling the mixture to-40 ℃,1' -dioxyphosphine chloride (6.6g, 26.3mmol, 2.5equiv.) is added dropwise into 60ml of anhydrous tetrahydrofuran solution, after completion of the addition, the reaction is carried out at room temperature for 24 hours, the reaction solution is concentrated under nitrogen atmosphere, and after separation by flash column chromatography, the crude product is recrystallized from acetonitrile to obtain 5.6g of the target product with a yield of 59%. ¹ H NMR(600MHz,CDCl ₃ ):δ＝1.42(d,36H),2.35(m,4H),3.18(m,4H),6.97– 7.10(m,8H),7.15(s,2H),7.30(td,4H),7.68(dd,4H)； ³¹ P NMR(243MHz,CDCl ₃ ): δ＝142.67。

Example 10: preparation of 7,7 '-bis [ (1, 1' -biphenyl-2, 2 '-diyl) phosphonite ] -4,4' -dimethoxy-6, 6 '-di-tert-butyl-1, 1' -spiroindane (6 a-L4)

The synthesis steps of the ligand 6a-L4 are similar to those of the intermediate 6-L4, 5.0g of the spirodiphenol 5a is added, 4.6g of the target product is finally obtained, and the yield is 46%. ¹ H NMR(600MHz,CDCl ₃ ):δ＝1.45(s,18H),2.37(m, 4H),3.02(m,4H),3.78(s,6H),6.70(s,2H),6.97–7.13(m,8H),7.30(td,4H),7.69 (dd,4H)； ³¹ P NMR(243MHz,CDCl ₃ ):δ＝140.59。

It is to be noted here that the other spirocyclic bisphosphonite ligands of the formula II, L1 to L31, can be prepared by using only different chlorophosphinite substituent derivatives.

After obtaining the target spiro diphosphonite ligand, a batch type small-scale reaction device (attached drawing in the specification) matched with the novel spiro diphosphonite ligand is developed to simulate the hydroformylation reaction of carbon four after mixing/etherification in industry. We used two separate carbon four feedstocks, the first is ether rear carbon four, and the component contents are respectively (w/w): isobutane (52.1%), 1-butene (16.6%), cis-2-butene (15.3%) and trans-2-butene (16.0%); the second is MTO carbon four, the component contents are respectively (w/w): n-butane (6.0%), 1-butene (0.7%), cis-2-butene (34.7%) and trans-2-butene (58.6%).

In order to ensure that the ligand activity and the aldehyde product are not oxidized, the materials pass through a raw material pretreatment device, and besides water removal, oxygen removal, sulfur (sulfide), chlorine (halide), nitrogen-containing compounds (such as HCN) and the like, substances such as carboxylic acid, butadiene, allene, alkyne and the like which have an inhibiting effect on a rhodium catalyst in the raw materials of carbon and carbon are also removed. To test the reactivity of the novel spirocyclic bisphosphinite Ligand in the post-ether/MTO carbon four, we tested other commercial and patent literature reported ligands under nearly identical reaction conditions in comparison, ligand Ligand 1-10 used in the following examples has the following structure:

this comparative example uses the spirocyclic bisphosphonites listed in the above examples as transition metal ligands to catalyze the hydroformylation of olefins as follows:

comparative example 1: adding a certain amount of Rh (acac) (CO) into a 200ml stainless steel high-pressure reaction kettle provided with a pressure sensor, a temperature probe, an online sampling port, a safety relief valve and the like under the argon atmosphere ₂ (0.01 mmol,2.6 mg) and a certain amount of Ligand Ligand 1-10 (0.03-0.04 mmol), adding a certain volume of toluene and internal standard substance n-decane, and stirring and complexing for 30 minutes by using a magneton to generate a catalytic complex of rhodium and the Ligand. Then, after connecting a gas pipeline and fully replacing, under the switching of a two-position four-way valve, adding a certain proportion of liquefied ether into the reaction kettle by using a plunger pump with a metering function, controlling the concentration of the rhodium catalyst in the total solution to be about 159ppm, and then uniformly stirring at room temperature for 5-10 minutes. After being stirred evenly, carbon monoxide and hydrogen are filled into the reaction deviceThe total pressure of the mixed gas (1. The reaction kettle is heated to the required temperature (70 ℃) by a magnetic stirrer (heating the bottom of the kettle) and an electric heating sleeve (heating the kettle body), and air is continuously supplied during the reaction to keep the total pressure constant at 1.0MPa. After reacting for 2-4 hours, the reaction kettle is connected to a-40 ℃ cold sleeve for cooling, after the kettle temperature is reduced to normal temperature, an online sampling port is opened for sampling under the condition of not opening the kettle, and after the online sampling port is diluted by chromatographic grade ethyl acetate, a Gas Chromatograph (GC) is used for measuring the normal-to-iso ratio (the ratio of n-valeraldehyde to 2-methyl butyraldehyde: l: b). And after the kettle is opened, completely releasing the gas in the high-pressure reaction kettle in a fume hood, and sampling and weighing. The results are shown in Table 1.

TABLE 1

Comparative example 2: adding a certain amount of Rh (acac) (CO) into a 200ml stainless steel high-pressure reaction kettle provided with a pressure sensor, a temperature probe, an online sampling port, a safety relief valve and the like in an argon atmosphere ₂ (0.01 mmol,2.6 mg) and a certain amount of Ligand Ligand 1-10 (0.03-0.04 mmol), adding a certain volume of toluene and internal standard substance n-decane, and stirring and complexing for 30 minutes by using a magneton to generate a catalytic complex of rhodium and the Ligand. Then, after connecting a gas pipeline and fully replacing, under the switching of a two-position four-way valve, adding a certain proportion of liquefied MTO carbon four into the reaction kettle by using a plunger pump with a metering function, controlling the concentration of the rhodium catalyst in the total solution to be about 159ppm, and then uniformly stirring at room temperature for 5-10 minutes. After stirring uniformly, a mixed gas (1. The reaction kettle is heated to the required temperature (70 ℃) by a magnetic stirrer (heating the bottom of the kettle) and an electric heating sleeve (heating the kettle body), and air is continuously supplied during the reaction to keep the total pressure constant at 1.0MPa. After reacting for 2-4 hours, the reaction kettle is connected to a-40 ℃ cold sleeve for cooling, and after the temperature of the kettle is reduced to normal temperature, the reaction kettle is cooledWithout opening the vessel, an on-line sampling port was opened to sample, and after dilution with chromatographic grade ethyl acetate, the normal-to-iso ratio (ratio of n-valeraldehyde/2-methylbutyraldehyde: l: b) was determined by Gas Chromatography (GC). And after the kettle is opened, completely releasing the gas in the high-pressure reaction kettle in a fume hood, and sampling and weighing. The results are shown in Table 2.

TABLE 2

Claims

1. The preparation method and the application of the spirocyclic diphenol and the diphosphonite thereof are characterized by comprising the following synthetic routes:

synthesis route of 4,4', 6' -tetra-tert-butyl-1, 1 '-spiroindane-7, 7' -diol：

Synthesis route of 4,4 '-dimethoxy-6, 6' -di-tert-butyl-1, 1 '-spiroindane-7, 7' -diol：

Wherein 6 or 6a can be represented by a general formula I, the spiro diphosphonite compound can be a racemate containing a symmetrical or asymmetrical structure, and can also be a compound containing optical activity or chirality, R represents a chlorophosphinite containing biphenyl, methylenebisphenyl, binaphthyl, benzoate, o-phenyl or phenyl, naphthyl, aryl and the like, and has the following structure:

2. the process for the preparation of a spirocyclic diphenol as claimed in claim 1, wherein: under the catalysis of protonic acid or Lewis acid, isobutene is added with protons to generate tert-butyl carbonium ions, and the tert-butyl carbonium ions are further alkylated with benzene rings on 3-hydroxybenzaldehyde or 5-hydroxy-2-methoxybenzaldehyde to obtain 2, 4-di-tert-butyl-5-hydroxybenzaldehyde (2) or 2-methoxy-4-tert-butyl-5-hydroxybenzaldehyde (2 a).

The protonic acid or Lewis acid used in the above reaction is one or more of organic acid or inorganic acid, and the organic acid is: formic acid, acetic acid, oxalic acid, dichloroacetic acid, trifluoroacetic acid, propionic acid, malonic acid, pyruvic acid, butyric acid, valeric acid, caproic acid, adipic acid, benzoic acid, p-nitrobenzoic acid, terephthalic acid, benzenesulfonic acid, fluorosulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, and the like; inorganic acids such as: hydrobromic acid, hydrochloric acid, hydrofluoric acid, sulfurous acid, sulfuric acid, perchloric acid, phosphonic acid, pyrophosphoric acid, nitric acid, nitrous acid, chromic acid, fluoroantimonic acid, and the like; the alkylating reagent is any one of bromo-tert-butane, chloro-tert-butane, isobutene and tert-butanol; the reaction temperature is 80-140 ℃, and the reaction solvent is any one of benzene, toluene, p-xylene, o-xylene, chlorobenzene or dichlorobenzene.

3. The process for the preparation of a spirocyclic diphenol as claimed in claim 1, wherein: the intermediate 2 or 2a and acetone are subjected to aldol condensation reaction to obtain 1, 5-bis (2, 4-di-tert-butyl-5-hydroxyphenyl) -1, 4-pentadien-3-one (3) or 1, 5-bis (2-methoxy-4-tert-butyl-5-hydroxyphenyl) -1, 4-pentadien-3-one (3 a).

The alkali used in the aldol condensation reaction is any one of potassium hydroxide, sodium hydroxide, potassium carbonate, sodium tert-butoxide and potassium tert-butoxide; the using amount of the alkali is 1.5 to 10 equivalents, the reaction solvent is ethanol or water or a mixed solvent thereof, the proportion of the mixed solvent is between 50 and 90 ℃, and the reaction temperature is 20 to 75 ℃.

4. The process for the preparation of a spirocyclic diphenol as claimed in claim 1, wherein: and (3) hydrogenating and reducing the carbon-carbon double bond of the intermediate 3 or 3a under the action of a reduction catalyst to obtain 1, 5-bis (2, 4-di-tert-butyl-5-hydroxyphenyl) -3-pentanone (4) or 1, 5-bis (2-methoxy-4-tert-butyl-5-hydroxyphenyl) -3-pentanone (4 a).

The catalyst used in the reduction reaction is any one of raney nickel, ferric chloride, cobalt oxide or palladium carbon; the catalyst is used in 1-20% (w/w), the hydrogen pressure is 0.05-5 MPa, the reaction temperature is 20-50 deg.c and the reaction time is 24-72 hr. The reaction solvent is any one of ethyl acetate, tetrahydrofuran, dichloromethane or 1, 4-dioxane.

5. The process for the preparation of spirocyclic diphenols as claimed in claim 1, wherein: the intermediate 4 or 4a is cyclized under the action of a dehydrating agent to obtain 4,4', 6' -tetra-tert-butyl-1, 1 '-spiroindane-7, 7' -diol (5) or 4,4 '-dimethoxy-6, 6' -di-tert-butyl-1, 1 '-spiroindane-7, 7' -diol (5 a).

The dehydrating agent used in the reaction is any one of polyphosphoric acid, concentrated sulfuric acid, acetic anhydride, methanesulfonic acid, benzoic acid, p-toluenesulfonic acid and anhydrous aluminum trichloride. The reaction solvent is any one of toluene, n-heptane, dichloromethane, trichloromethane and dichloroethane. The dosage of the dehydrating agent is 10 to 70 equivalent, the reaction temperature is 45 to 135 ℃, and the reaction time is 2 to 6 hours.

6. A process for the preparation of a spirocyclic bisphosphinite compound according to claim 1, characterized in that:

sequentially adding the intermediate 4 or 4a and an organic solvent into a reaction container under the nitrogen atmosphere to obtain a first mixed solution; or sequentially adding the intermediate 4 or 4a and an organic solvent into the reaction container in the nitrogen atmosphere, dropwise adding n-butyl lithium at low temperature, heating to room temperature after dropwise adding, and performing reflux reaction to obtain a lithiated first mixed solution;

and (2) dropwise adding biphenyl, methylene diphenyl, binaphthyl, benzoate, o-phenyl, or a mixed solution of chlorophosphonites containing phenyl, naphthyl, aryl and the like and an acid-binding agent or an organic solution of the above listed chlorophosphonites into the first mixed solution or the lithiated first mixed solution at low temperature, reacting at room temperature after dropwise adding, processing inorganic salt, and concentrating to obtain a crude product of the ligand 6 or 6 a.

In the esterification reaction, the using amount of n-butyl lithium is 2-4 equivalents; the acid-binding agent is any one of triethylamine, N-diisopropylethylamine and pyridine, and the dosage is 5-20 equivalent; the reaction temperature is-78-80 ℃, the reaction time is 12-48 hours, and the reaction solvent is any one of toluene, tetrahydrofuran, diethyl ether, 2-methyl tetrahydrofuran, methyl tert-butyl ether, isopropyl ether, anisole, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, butyl ether, cyclopentyl methyl ether or 1, 4-dioxane.

7. The process for the preparation of a spirocyclic bisphosphinite compound according to claim 6, characterized in that: the solvent for recrystallizing and purifying the spiro diphosphonite compound 6 or 6a is any one or more of ethyl acetate, toluene, dichloromethane, ethanol, acetonitrile, petroleum ether, n-hexane and tetrahydrofuran.

8. Process for the preparation of spirocyclic diphenols and their bisphosphinites according to claims 1 and 6, characterized in that: said spirodiphenol may be (±) -spirodiphenol, (+) -spirodiphenol or (-) -spirodiphenol; the spiro diphosphonite compound can be a (+/-) -spiro diphosphonite compound, a (+) -spiro diphosphonite or a (-) -spiro diphosphonite compound, and the chiral spirodiphenol compound can realize efficient resolution by adopting proline, menthyl chloroformate or a chiral phase transfer catalyst N-benzylcinchonine chloride as a resolution reagent.

9. A catalytic complex characterized by: the catalytic complex comprises a transition metal precursor (e.g., rh, pt, pd, ru, ir, etc.) and a racemic spirocyclic bisphosphinite ligand comprising all ligands listed in formula I of claim 1 except for (R, S) -L12, (R, S) -L13, (R, S) -L17, and (R, S) -L31. In addition, the catalytic complex comprises a transition metal precursor (such as Rh, pt, pd, ru, ir, etc.) and a chiral spiro bisphosphinite ligand comprising L1 to L31 listed in formula I of claim 1.

10. A process for the hydroformylation of olefins to produce linear aldehydes, characterized in that: the preparation method comprises the step of reacting olefin with synthesis gas in the presence of the catalytic complex of claim 9 to obtain the linear aldehyde. The method can be realized according to the following process steps and parameters;

(1) Sequentially adding a racemic spiro diphosphonite ligand and a rhodium catalyst in a certain proportion in a reaction device under the protection of inert gas, wherein the molar ratio of phosphine to rhodium is 1;

(2) Then, under the protection of inert gas, adding liquid ether with a certain proportion into the reaction kettle by using a plunger pump with a metering function, controlling the concentration of the rhodium catalyst at about 50-200 ppm, and then uniformly stirring for 5-10 minutes at room temperature.

(3) After stirring uniformly, filling CO and H with a certain pressure into the reaction device ₂ The pressure ratio of hydrogen to carbon monoxide is between 1 and 1; stirring and reacting for 1-4 hours at the temperature of 40-100 ℃.

The post-ether carbon four and the MTO carbon four used in the hydroformylation reaction comprise the following components in percentage by mass: 0-30% of 1-butene, 0-70% of trans-2-butene, 0-40% of cis-2-butene, 0-30% of n-butane, 0-20% of isobutane and 0-10% of isobutene, wherein the total mass percent of the 1-butene, the trans-2-butene, the cis-2-butene, the n-butane, the isobutane and the isobutene is 100%.