WO2015181415A1

WO2015181415A1 - Synthesis of copper (i) and silver (i) complexes with a fluorinated trispyrazolylborate ligand and the use thereof in the functionalisation of alkanes

Info

Publication number: WO2015181415A1
Application number: PCT/ES2015/070397
Authority: WO
Inventors: Andrea OLMOS VERGÉ; Bárbara NOVERGES PEDRO; Riccardo GAVA; Ana CABALLERO BEVIA; Gregorio Asensio Aguilar; Pedro José PÉREZ ROMERO
Original assignee: Universitat De València; Universidad De Huelva
Priority date: 2014-05-28
Filing date: 2015-05-20
Publication date: 2015-12-03
Also published as: ES2555331B1; ES2555331A1

Abstract

The invention relates to catalysts of general formula Tp ^(CF3)2,Br M L, where M is a metal in a state of oxidation +1 selected from copper and silver and L is a solvent selected from acetonitrile or tetrahydrofurane. The invention also relates to the use of same for inserting diazo compounds into the carbon-hydrogen bonds of alkanes and and to the method for the synthesis of said catalysts.

Description

DESCRIPTION

SYNTHESIS OF COPPER (I) AND SILVER (I) COMPLEXES WITH A FLUORED TRISPIRAZOLILBORATE BINDING AND ITS USE IN THE FUNCTIONALIZATION OF ALCANOS Field of the Invention

The present invention fits in general, in the field of organometallic chemistry and catalysis, and in particular describes the synthesis of copper (I) and silver (I) complexes that contain in their coordination sphere a new trispyrazolylborate ligand and its use in the catalytic functionalization of alien. State of the art

The conversion of alien, simple and low-cost molecules, in others with a certain added value is of great interest to the petrochemical industry. A methodology described in the specialized literature consists of the insertion of diazo compounds (N ₂ CR ¹ CR ² ) in the carbon-hydrogen bonds of the aliens, which implies the addition of the CR ¹ CR ^{2 unit} to the alkane molecule. This process requires the presence of a compound of some transition metal that catalyzes the transformation. Examples of this class of functionalization reactions of aliens are scarce in the literature, and in general, provide moderate yields. In addition, there are few known systems for the functionalization of primary bonds and none of them (with the exception of one) allows the functionalization of the CH bonds of methane, the less reactive alkane due to its greater bond dissociation energy.

The most active catalysts described so far contain rhodium (Davies, J. Am. Chem. Soc. 2000, 122, 3063), copper (Pérez, J. Am. Chem. Soc. 2003, 125, 1446), silver (Pérez Romero, Patent ES2253088; Pérez and Díaz-Requejo Organometallics 2005, 24, 1528; Dias, Organometallics 2004, 24, 1528; Asensio, Etienne and Pérez, Science 201 1, 332, 835; Caulton and Mindiola ACS Catal. 2012, 2, 2066; Caballero, Etienne and Pérez, Chem. Eur. J. 2013, 19, 1327) and gold (Nolan, Díaz-Requejo and Pérez, Angew. Chem. Int. Ed. 2005, 44, 5284, Pérez Romero, Patent ES270706 ). The work done with these last three metals has used ethyl diazoacetate (hereinafter EDA) as a diazo compound, a substance used in i Various business processes. However, such compounds are not valid in reactions that use gaseous aliens at room temperature.

In addition, there is a collateral reaction that takes place in this type of reactions in which diazo compounds and transition metals are used and is the catalytic decomposition of the latter to form olefins derived from the coupling of two diazo compounds. Thus, for example, EDA decomposes very easily in the presence of catalysts of the aforementioned metals to give a mixture of fumarate and diethyl maleate. This reaction must be minimized to increase the yields of the desired products, in this case those derived from the insertion in the CH bonds of the alien. It is therefore desirable to have catalysts that allow to apply the above methodology to CH methane bonds and primary links CH simple alkanes of the general formula C _n H _2n ₊ 2, which have a high chemoselectivity, understood as a high proportion of the desired products on those derived from the dimerization reaction of the corresponding diazo compound, with high yield and with improved turnover numbers or catalyst turns with respect to the existing ones.

The present invention solves the problems set forth in the state of the art since it provides a compound that acts as a catalyst in the insertion reactions of diazo compounds in the carbon-hydrogen bonds of the aliens, allowing its functionalization with high chemoselectivity and high yields. . Description of the invention

Thus, in a first aspect, the present invention relates to a compound of general formula (I), Tp ^{(CF3) 2 Br} ML, (hereinafter compound of the present invention), wherein

Tp is a tris (4-bromo-3,5-bis (trifluoromethyl) pyrazol-1-yl) borate ligand, M is a +1 oxidation metal selected from copper or silver,

Ligand L is an aprotic solvent selected from acetonitrile, tetrahydrofuran or acetone The compound of the present invention is also represented by the following general formula:

In a preferred embodiment, the metal M of the compound of the present invention is silver and the solvent L is tetrahydrofuran. In particular the compound is Tp ^{(CF3) 2 Br} Ag-THF.

In another preferred embodiment, the metal M of the compound of the present invention is copper and the solvent L is acetonitrile. In particular, the compound is Tp ^{<CF3) 2 Br} Cu-NCCH ₃

In another aspect, the present invention relates to the use of the compound of the present invention as a catalyst for the conversion of alkanes of the general formula C _n H _{2n +} 2 into C _n H _{2n + 2} CR ¹ CR ² alkanes by inserting diazo compounds of general formula N ₂ CR ¹ CF? in the carbon-hydrogen bonds of alkanes.

In a preferred embodiment of the present invention, the diazo compound is ethyl diazoacetate.

In a preferred embodiment, the insertion of ethyl diazoacetate in the carbon-hydrogen bond of the alkane of the general formula C _n H _{2n +} 2 gives rise to an ester of the general formula

In a preferred embodiment R ¹ and R ² are independently selected from the group consisting of alkanes, alkynes, phenyls.

In a particular embodiment, the conversion of alkanes is carried out at temperatures between 20 and 40 ° C.

In a particular embodiment, the conversion of alkanes is carried out with a molar ratio between the catalyst and the diazo compound between 1: 50 and 1: 100. In a particular embodiment, the conversion of alloys is carried out using pure alkane as a reaction medium or a mixture of the alkane with carbon dioxide.

In another aspect, the present invention relates to a process for preparing the compound of the present invention (hereinafter, process of the present invention) comprising the following steps: a) reacting ethanol with hydrazine and 1, 1, 1, 5,5,5-hexafluoropenta-2,4-dione to give rise to a mixture of 3,5-bis (trifluoromethyl) pyrazolidine-3,5-diol diastereomers, b) the compound obtained in step a) is made reacting with phosphorus pentoxide and dichloromethane to obtain 3,5-bis (trifluoromethyl) pyrazole, c) the compound obtained in step b) is reacted with bromine in basic medium to obtain 4-bromo-3,5-bis (trifluoromethyl) pyrazole after acidification of the reaction medium. d) the compound of step c) is reacted with thallium borohydride to obtain tris (4- bromo-3,5-bis (trifluoromethyl) pyrazol-1-yl) boium, e) the compound obtained in step d ) is reacted with a metal complex and a solvent to give rise to the compound of formula generates Tp ^{(CF3) 2 Br} ML

In a preferred embodiment, in step e) of the process of the present invention, copper iodide is added as metal and acetonitrile as solvent to obtain tris (4-bromo-3,5-bis (trifluoromethyl) pyrazol-1-yl) copper borate

In another preferred embodiment, in step e) of the process of the present invention, AgOTf is added as a metal complex and tetrahydrofuran as solvent to obtain tris (4- bromo-3,5-bis (trifluoromethyl) pyrazol-1-yl) borate silver.

Detailed description of the invention

All reactions and manipulations were carried out under an inert atmosphere of nitrogen, free of oxygen, using Schlenk techniques. The solvents were dried and stored under an inert atmosphere before use. The reactions involving silver salts were carried out protected from light. The 3,5-bis (trifluoromethyl) pyrazole pyrazoles (McCIeverty, J. Fluorine Chem. 1991, 51, 283; Threadgill, J. Fluorine Chem. 1993, 65, 21; Gerus and Mykhailiuk, J. Org. Chem. 2012, 77, 47) and 4-bromo-3,5-bis (trifluoromethyl) pyrazole (Maspero, J. Fluorine Chem. 2012, 139, 53) were previously prepared. However, new preparation processes are described in the present invention which allow them to be obtained with a higher yield. Thallium borohydride (Kitamura, Eur. J. Inorg. Chem. 2008, 8, 1 188) was prepared following the procedure described in the literature.

EXAMPLE 1: Synthesis of complexes with the general formula (I).

^{0 0} ΝΗ, ΝΗ, -Η, Ο, EtOH,

¹⁾ _F F _3C CAA _CF _ ₀ ° ca T. amb., 1 h - ^F s ^{cv 0H + F} 3 ^C O ^{v CF} s

60% 40%

Scheme 1: Synthesis of compounds of general formula (1). Synthesis of 3,5-bis (trifluoromethyl) pyrazole In a round bottom flask of two 250 ml mouths, 90 ml of EtOH were added and cooled to -10 ° C. 0.72 ml_ (15 mmol) of ΝΗ ₂ ΝΗ ₂ Ή ₂ 0 was added, after stirring 15 min at that temperature 2.10 ml_ of 1, 1, 1, 5,5,5-hexafluoropenta-2,4-dione (slowly added) 15 mmol) over a period of 30 minutes. When the addition was finished the mixture was brought to room temperature. After two hours at room temperature the starting diketone was completely consumed. EtOH was evaporated in vacuo to form a clear oil. The oil was diluted in Et ₂ 0 and washed with brine in extraction funnel. The organic extract was dried over Na ₂ S0 ₄ and filtered on filter plate. Et ₂ 0 was evaporated leaving a white solid corresponding to the mixture of 3,5-bis (trifluoromethyl) pyrazolidine-3,5-diol diastereoisomers which was subsequently dried under vacuum (100% yield).

In an ampoule they were dissolved a70 Caproximadamente ^2, 3.60 g of the above diastereomeric mixture (15 mmol) and added to 10 mL of CH ₂ Cl _2. Next, 2.16 g of P ₂ 0 ₅ (15 mmol) and 10 mL of CH ₂ CI _{2 were added} and the vial was closed. The mixture was heated at 80 ° C for 3 hours. Once at room temperature, the mixture was transferred to an extraction funnel dissolving the viscous phase, formed by phosphorus pentoxide, with a saturated solution of NaHC0 ₃ and the ampoule was washed. with CH ₂ CI ₂ . NaHC0 _{3 was} added until the mixture was neutralized and extracted with CH ₂ CI ₂ three times. The dichloromethane phases were combined, dried over Na ₂ S0 ₄ , filtered on a filter plate and dried on the rotary evaporator with an H ₂ 0 / ice bath to obtain a white solid corresponding to 3,5-bis (trifluoromethyl). ) -1 H-pyrazole (yield = 94-98%).

The spectroscopic data for 3,5-bis (trifluoromethyl) pyrazole were as follows: ¹ H NMR (300 MHz, CDCI ₃ , 20 ° C), δ (ppm): 9.73 (bs), 6.94 (s); ¹⁹ F NMR (280 MHz, CDCI ₃ , 20 ° C), δ (ppm): -62.48 (s); ¹³ C NMR (75 MHz, CDCI ₃ , 20 ° C), δ (ppm): 139.5 (q, = 40.8Hz), 1 19.67 (q, = 268.7Hz), 104.59.

Synthesis of 4-bromo-3,5-bis (trifluoromethyl) pyrazole

In a 250 mL round bottom flask, 6.00 g of 3,5-bis (trifluoromethyl) pyrazole (30 mmol) was dissolved in 80 mL of an aqueous solution of 1.2 M NaOH in an ice bath. Then, 1.7 mL of bromine (33 mmol) was added with the help of a compensated addition funnel. After the addition, the reaction mixture was brought to room temperature. After three hours of stirring at room temperature, the reaction mixture was carefully acidified with concentrated hydrochloric acid to pH 4-5. The yellowish precipitate formed was filtered and washed with distilled water 3 times. The product was dissolved in CH ₂ CI ₂ , washed with distilled H ₂ 0 and dried over Na ₂ S0 ₄ . The CH ₂ CI ₂ was filtered and evaporated leaving a white solid corresponding to 4- bromo-3,5-bis (trifluoromethyl) pyrazole. The product could be recrystallized from hexane and dried in a desiccator with phosphorus pentoxide. (Yield 85-90%).

The spectroscopic data for 4-bromo-3,5-bis (trifluoromethyl) pyrazole were as follows: ¹ H NMR (500 MHz, CDCI ₃ , 20 ° C), δ (ppm): 12.75 (bs, 1 H); ¹⁹ F NMR (470 MHz, CDCI3, 20 ° C), δ (ppm): -62.12 (s); ¹³ C NMR (125 MHz, CDCI ₃ , 20 ° C), δ (ppm): 138.4 (q, J = 37.3Hz), 1 19.3 (q, J = 270Hz), 93.3.

Synthesis of tris (4-bromo-3,5-bis (trifluoromethyl) pyrazol-1-yl) thallium borate (Τρ '^' ^ ΎΠ

In a Fisher-Porter reactor, 1.41 g of 4-bromo-3,5-bis (trifluoromethyl) pyrazole (5 mmol) and 275 mg of thallium borohydride (1.25 mmol) were introduced. The mixture was heated under stirring under a nitrogen atmosphere slowly to 140 ° C. After one hour the temperature was raised to 170 ° C and the reactor was closed. After three hours the heating was stopped and, once at room temperature, the solid residue obtained was dissolved in chloroform and filtered. If necessary, the product can be purified by recrystallization of chloroform. (Yield 75-80%).

The spectroscopic data obtained for thallium tris (4-bromo-3,5-bis (trifluoromethyl) pyrazol-1-yl) borate were as follows: ¹ H NMR (500 MHz, CDCI ₃ , 20 ° C), δ (ppm ): 5.06 (d, = 122.7Hz, 1 H); ¹⁹ F NMR (470 MHz, CDCI ₃ , 20 ° C), 5 (ppm): -57.13 (d, = 3.5Hz), -60.03 (d, = 972.0Hz); ¹³ C NMR (125 MHz, CDCI ₃ , 20 ° C), δ (ppm): 143.0 (qd, = 36.1 Hz, = 18.1 Hz), 139.0 (q, J = 39.5Hz), 120.72 (qd, = 269.7Hz , = 1 1 .5Hz), 1 19.1 (q, = 269.7Hz), 95.0. ¹¹ B NMR (160 MHz, CDCI ₃ , 20 ° C), δ (ppm): -4.48. Analytical data: Anal. Caled, for Ci ₅ HBBr ₃ F ₁₈ N ₆ TI: C 16.96, H 0.09, N 7.91. Experimental: C 16.66, H 0.04, N 9.21.

Synthesis of tris (4-bromo-3,5-bis (trifluoromethyl) Dirazol-1-yl) copper borate (Tp ^{(CF3) 2 Br} Cu-NCCH)

On a solution of 38 mg of Cul (0.2 mmol) in 5 mL of acetonitrile was added a solution of 212 mg of Tp ^{(CF3) 2 Br} TI (0.2 mmol) in 5 mL of acetonitrile. The resulting solution was stirred at room temperature for 15 hours before being dried in vacuo. The resulting solid was extracted with n-hexane (3x7 mL). The extracts were combined and dried in vacuo to give a white solid. If necessary, the product can be recrystallized from acetonitrile. (Yield 75%). The spectroscopic data for tris (4-bromo-3,5-bis (trifluoromethyl) pyrazol-1-yl) copper borate were as follows: ¹ H NMR (500 MHz, CDCI ₃ , 20 ° C), δ (ppm) : 5.07 (d, = 93.6Hz, 1 H), 2.17 (s, 3H); ¹⁹ F NMR (470 MHz, CDCI ₃ , 20 ° C), δ (ppm): -56.41 (d, = 4.5Hz), -61 .26 (s); ¹³ C NMR (125 MHz, CDCI ₃ , 20 ° C), δ (ppm): 142.1 (q, = 37.5Hz), 137.8 (q, = 40.0Hz), 1 19.8 (q, = 270.9Hz), 1 19.1 (q, = 272.6Hz), 1 14.1, 94.7, 2.47. ¹¹ B NMR (160 MHz, CDCI ₃ , 20 ° C), δ (ppm): -6.58. Analytical data: Anal. Caled, for C ₁₇ H ₄ BBr ₃ CuF ₁₈ N ₇ : C 21 .22, H 0.42, N 10.19. Experimental: C 20.92, H 0.32, N 1 1 .56.

Synthesis of tris (4-bromo-3,5-bis (trifluoromethyl) pyrazol-1-yl) silver borate (Tp ^{(CF3) 2 Br} Aq-THF)

On a solution of 51 mg of AgOTf (0.2 mmol) in 5 mL of tetrahydrofuran was added a solution of 212 mg of Tp ^{(CF3) 2, Br} TI (0.2 mmol) in 5 mL of tetrahydrofuran. The resulting solution was stirred at room temperature for 5 hours before being dried in vacuo. The resulting solid was extracted with n-hexane (3x7 mL). The extracts were combined and dried in vacuo to give a white solid. If necessary, the product can be recrystallized from tetrahydrofuran. (Yield 70%). The spectroscopic data for silver tris (4-bromo-3,5-bis (trifluoromethyl) pyrazol-1-yl) borate were as follows: ¹ H NMR (500 MHz, CDCI ₃ , 20 ° C), δ (ppm) : 6.09 (d, = 87.6Hz, 1 H), 3.93 (m, 4H), 1.99 (m, 4H); ¹⁹ F NMR (470 MHz, CDCI ₃ , 20 ° C), δ (ppm): -56.81 (s), -62.22 (s); ¹³ C NMR (125 MHz, CDCI ₃ , 20 ° C), 5 (ppm): 143.0 (q, = 36.0Hz), 138.7 (q, = 39.7Hz), 1 19.9 (q, = 270.5Hz), 1 19.1 (q, = 273.2Hz), 94.4, 71 .6, 25.8. ¹¹ B NMR (160 MHz, CDCI ₃ , 20 ° C), δ (ppm): -5.53. Analytical data: Anal. Caled, for Ci ₉ H ₉ AgBBr ₃ F ₁₈ N ₆ : C 21 .99, H 0.87, N 8.10. Experimental: C 21 .64, H 0.42, N 8.51.

EXAMPLE 2: Reaction of ethyl diazoacetate with alloys in the presence of the compounds of general formula (1) as catalysts.

Reactions carried out using pure alkane as a reaction medium In a schlenck flask, 0.005 mmol of complex in 5 mL of the corresponding alkane was dissolved under stirring. Then 57 μΐ of EDA (0.5 mmol) were added. The reaction was stirred 3 hours at room temperature. The conversion and yield of the reactions was determined by gas chromatography analysis. These data were corroborated by proton NMR using 1,4-dimethoxybenzene as internal standard. Reactions carried out using as a reaction medium mixtures of gaseous alkanes and CO?

In a high pressure reactor with a capacity of 33 mL, 0.005 mmol of catalyst were introduced into a polypropylene container with both permeable ends and 0.5 mmol of EDA in a second open container. The reactor was cooled to 0 ° C in an ice bath and connected to a pressurized bottle of the desired gas for the time necessary to introduce between 3 and 5 g of alkane. The reactor was then introduced into a thermostated ultrasonic bath at 40 ° C and, after stabilizing the temperature, C0 ₂ was pumped into the reactor to a total pressure of 250 atm. The exact amount of alkane used was determined by weighing the reactor before and after pressurization. The reactor was sonic in the ultrasonic bath for 4 hours before the analysis of the reaction mixture by means of a gas chromatograph connected in line. The reaction yield was determined by calibration curves constructed using samples of commercial products. As an example, table 1 shows the results obtained with the catalyst

_Tp (CF3) 2, Br _Ag . _THF

Table 1 .

reaction. ^b Reactions carried out in pure alkane.

Claims

one . Compound of general formula (I)

_Tp (CF3) 2, Br _ML where Tp ^{(CF3) 2 Br} is a tris (4-bromo-3,5-bis (trifluoromethyl) pyrazol-1-yl) borate ligand, M is a metal in oxidation state +1 selected from copper or silver,

L is a ligand selected from the aprotic solvents acetonitrile, tetrahydrofuran or acetone.

2. Compound of general formula (I) according to claim 1, characterized in that the metal M is silver and the ligand L is tetrahydrofuran

3. Compound of general formula (I) according to claim 1, characterized in that the metal M is copper and the ligand L is acetonitrile.

4. Use of the compound of general formula (I) according to any of the preceding claims as a catalyst in functionalization reactions of alkanes of general formula C _n H ₂ n ₊ 2 for conversion into alkanes C _n H _{2n + 2} CR ¹ CR ² by inserting diazo compounds of the general formula N ₂ CR ¹ CR ² into the carbon-hydrogen bonds of the alkanes.

5. Use according to claim 4, characterized in that R ¹ and R ² are independently selected from the group consisting of alkanes, alkynes or phenyls.

6. Use according to claim 5, characterized in that the diazo compound is ethyl diazoacetate.

7. Use according to any of claims 4-6, characterized in that the alkane is methane.

8. Use according to any of claims 4-7, characterized in that the functionalization reaction is carried out at a temperature between 20-40 ² C.

9. Use according to any of claims 4-8, characterized in that the molar ratio between the catalyst and the diazo compound is comprised between 1: 50-1: 100.

10. Use according to any of claims 4-9, characterized in that the reaction medium is selected from pure alkane or alkane with carbon dioxide.

eleven . Process for preparing the compound of general formula (I) according to claims 1 - 3, characterized in that it comprises the following steps: a) reacting ethanol with hydrazine and 1, 1, 1, 5,5,5-hexafluoropenta-2,4- dione to give a mixture of 3,5-bis (trifluoromethyl) pyrazolidine-3,5-diol diastereomers, b) the compound obtained in step a) is reacted with phosphorus pentoxide and dichloromethane to obtain 3, 5- bis (trifluoruromethyl) pyrazole, c) the compound obtained in step b) is reacted with bromine in basic medium to obtain 4-bromo-3,5-bis (trifluoromethyl) pyrazole. d) the compound of step c) is reacted with thallium borohydride to obtain tris (4- bromo-3,5-bis (trifluoromethyl) pyrazol-1-yl) boium, e) the compound obtained in step d ) is reacted with a metal complex and a solvent to give rise to the compound of formula generates Tp ^{(CF3) 2 Br} ML

12. Method according to claim 1, characterized in that in step e) copper iodide is added as a metal complex and acetonitrile as solvent to obtain tris (4- bromo-3,5-bis (trifluoromethyl) pyrazol-1-yl ) copper borate

13. Process according to claim 1, characterized in that in step e) AgOTf is added as a metal complex and tetrahydrofuran as solvent to obtain tris (4-bromo-3,5-bis (trifluoromethyl) pyrazol-1-yl) borate silver.