Laboratory Experiment pubs.acs.org/jchemeduc
Synthesis of Dichlorophosphinenickel(II) Compounds and Their Catalytic Activity in Suzuki Cross-Coupling Reactions: A Simple AirFree Experiment for Inorganic Chemistry Laboratory Todsapon Thananatthanachon* and Michelle R. Lecklider Department of Chemistry, University of Evansville, Evansville, Indiana 47722, United States S Supporting Information *
ABSTRACT: In this experiment, students perform an air-free synthesis of three dichlorophosphinenickel(II) compounds, NiCl2(PPh3)2, NiCl2(PCy3)2, and NiCl2(DPPE), using NiCl2· 6H2O and the appropriate phosphine as the precursors. These colorful nickel compounds are air-sensitive in solution, but are stable toward air once isolated in the solid form. The synthesized nickel products will be utilized in a catalytic Suzuki cross-coupling reaction between phenylboronic acid and 1-bromo-4-(trifluoromethyl)benzene. The formation of the desired product, 4-(trifluoromethyl)biphenyl, is observed and determined quantitatively by 19F{1H} NMR spectroscopy. The effect of the phosphine ligands on the formation of the nickel products and their catalytic activity will also be determined. KEYWORDS: Second-Year Undergraduate, Inorganic Chemistry, Hands-On Learning/Manipulatives, Laboratory Instruction, Synthesis, Catalysis, Coordination Compounds, NMR Spectroscopy, UV−Vis Spectroscopy
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BACKGROUND Catalysis is an essential process that is widely used in chemical synthesis.1 It is a critical component of the 12 Principles of Green Chemistry,2 and improves the efficiency of the reactions by means of enhancing the reaction rates. Currently, more than 75% of all industrial processes including hydrocracking (oil refinery),3 olefin polymerization (plastic production),4 and hydrogenation (food industry)5 require the use of catalysts.6 Catalysts increase the rate of reaction by lowering the activation energy due to the formation of stable intermediates. Furthermore, catalysts are not consumed by the reaction and are regenerated once the reaction is complete; therefore, only a small quantity of catalyst is required. However, the major drawback of the current catalytic processes is the dependence on expensive precious metals such as Pd, Pt, Ru, Ir, and Rh,7 which results in a high operational cost. Therefore, attention from recent research has been focused on the incorporation of an inexpensive and abundant first-row transition metal such as Ni, Fe, Cu, and Co.8 Suzuki cross-coupling between organoboron compounds and organohalides is the most common reaction for a C−C bond formation,9 which has been widely utilized in the pharmaceutical industry.10 Unfortunately, the reactions are typically catalyzed by expensive Pd catalysts. For example, mesitylboronic acid and iodobenzene undergo a C−C cross-coupling reaction in a presence of Pd(PPh3)4 and a strong base to produce the biaryl product A in excellent yield under mild reaction conditions (Scheme 1).11 © XXXX American Chemical Society and Division of Chemical Education, Inc.
Scheme 1. Suzuki Cross-Coupling Using Pd(PPh3)4 Catalyst
More recently, nickel-based catalysts have been successfully utilized as an effective catalyst for Suzuki cross-coupling reactions. Zim et al. employed NiCl2·6H2O in a cross-coupling reaction between phenylboronic acid and substituted aryl bromides in a presence of K3PO4 at 130 °C to form the desired products in moderate to excellent yields (6−87%).12 Ramgren et.al. utilized NiCl2(PCy3)2 in a reaction between aryl halides and aryl boronic acids in the presence of K3PO4 at 100 °C.13 The products were obtained in excellent yields. As afo rementio ned , four-coord inated d ichlo rophosphinenickel(II), NiCl2(PR3)2, compounds have been demonstrated as efficient catalysts for Suzuki cross-coupling reactions. These colorful nickel compounds are not only attractive toward these cross-coupling reactions due to their high reactivity, but they are also air-stable in the solid form. Furthermore, they can be easily prepared from the inexpensive NiCl2·6H2O precursor and the appropriate phosphine (eq 1).14 Received: April 12, 2016 Revised: March 8, 2017
A
DOI: 10.1021/acs.jchemed.6b00273 J. Chem. Educ. XXXX, XXX, XXX−XXX
Journal of Chemical Education NiCl 2· 6H 2O + 2PR3 → NiCl 2(PR3)2 R = alkyl, aryl
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Laboratory Experiment
EXPERIMENT
This experiment requires one 3 h laboratory period. Students could work individually or in a small group. The experimental procedure can be modified so that students perform part of the experiment and share the results with other students (or groups of students). There are two main parts of this experiment: (i) the synthesis of three dichloronickel(II) catalysts equipped with phosphine ligands of different steric and electronic properties, NiCl2(PPh3)2, NiCl2(PCy3)2, and NiCl2(DPPE), and (ii) the catalysis of the prepared catalysts in a Suzuki cross-coupling reaction. Students assemble the primitive air-free apparatus using rubber tubings, a Y gas splitter, a disposable Pasteur pipet, and a test tube partially filled with vegetable oil. The assembled airfree apparatus is then connected to a 100 mL two-neck reaction flask equipped with a reflux condenser. A picture of the assembled apparatus is presented in Supporting Information S12 and S13. The synthesis begins with addition of NiCl2· 6H2O and the appropriate phosphine in the reaction flask, which is purged with a constant flow of N2 gas to ensure that all of the air is removed. Ethanol is then quickly added to the reaction flask, and the reaction mixture is heated at reflux. Since these dichlorophosphinenickel(II) compounds are colorful and are insoluble in ethanol, the progress of the reactions can be monitored visually by the color change and the formation of precipitate. The desired dichlorophosphinenickel(II) products are air-stable in the solid form, and are conveniently collected by filtration using a Buchner funnel. The synthesized solids are further characterized by UV−vis spectroscopy in CH2Cl2. The second part of the experiment involves the catalysis of the prepared nickel compounds in a Suzuki cross-coupling reaction between 1-bromo-4-(trifluoromethyl)benzene and phenylboronic acid to form 4-(trifluoromethyl)biphenyl (Scheme 2).
(1)
Coordination chemistry is a topic typically covered in an introductory or intermediate level of inorganic chemistry curriculum, which is taken by lower-division students of various majors such as chemistry, biochemistry, and the preprofessional tracks. Most of the experiments involving the synthesis of coordination compounds are carried out in air. However, airfree synthesis experiments are uncommon for an inorganic chemistry laboratory of this level due to a high cost of the apparatus (Schlenk line) and complicated experimental procedures. Recently, a laboratory experiment involving an air-free synthesis of iron-PNNP catalysts was published in 2015.15 However, this experiment requires extensive preparation time by the instructor to synthesize the ligand precursor. A laboratory experiment on the catalytic Suzuki cross-coupling reactions by NiCl2(PCy3)2 has been recently developed.16 This experiment is aimed for an organic chemistry laboratory, where various boronic acid substrates are employed and the percent yields of the products were obtained by 1H NMR spectroscopy. The experiment does not involve synthesis of the nickel catalyst. An experiment involving the synthesis of NiCl2(DPPE) from NiCl2·6H2O and DPPE in ethanol has been developed by Girolami, Rauchfuss, and Angelici.17 The compound is analyzed by IR and 1H NMR spectroscopy. This novel experiment is focused on the air-free synthesis of three dichlorophosphinenickel(II) compounds, and their catalytic activity in the Suzuki cross-coupling between phenylboronic acid and 1-bromo-4-(trifluoromethyl)benzene under nitrogen atmosphere. The synthesis part of this experiment is straightforward, and all of the chemicals are easily accessible and inexpensive. To perform the air-free synthesis, only a primitive air-free apparatus, which can be easily assembled in the laboratory from common glassware, is required. Furthermore, both the substrate employed in the cross-coupling reaction, 1-bromo-4-(trifluoromethyl)benzene, and the desired biaryl product contain fluorine atoms, which conveniently allows (i) the progress of the reaction to be monitored, and (ii) the percent conversion of the product as well as the turnover number (TON) of the catalyst to be quantified by 19F{1H} NMR spectroscopy.
Scheme 2. Suzuki Cross-Coupling Reaction of 1-Bromo-4(trifluoromethyl)benzene and Phenylboronic Acid
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PEDAGOGICAL GOALS The experiment introduces the concept of air-free synthesis of coordination compounds and their application in homogeneous catalysis. Both air-free techniques and catalytic processes are essential components in chemistry, but they are mostly excluded from the inorganic chemistry curriculum until the advanced level. The pedagogical goals of this experiment follow. • Students will be familiar with the techniques and equipment used for an air-free synthesis of coordination compounds. • Students will understand a concept and realize the impact of catalytic processes. • Students will be able to utilize heteronuclear (19F{1H}) NMR spectroscopy to determine the percent conversion of the desired product and the TON of the catalyst from the catalytic reactions. • Students will be able to determine the effect of different phosphine ligands in the formation and the catalytic activity of the synthesized nickel compounds.
The prepared catalyst, K3PO4, and phenylboronic acid are added to a two-neck round-bottom flask equipped with a reflux condenser, which is connected to the assembled air-free apparatus. The flask is purged again with N2 gas, followed by an addition of t-amyl alcohol and 1-bromo-4-(trifluoromethyl)benzene. The reaction mixture is heated at reflux overnight. The final mixture is analyzed by 19F{1H} NMR spectroscopy, where the students determine the percent conversion of the 4(trifluoromethyl)biphenyl product, and TON of the catalyst from the relative integrations (I) of the signals of the product and the unreacted substrate (eqs 2 and 3). Iproduct % conversion = × 100 Iproduct + Isubstrate (2)
TON =
Mol product Molcatalyst
(3)
A reference catalysis run is also performed using NiCl2·6H2O as a catalyst. B
DOI: 10.1021/acs.jchemed.6b00273 J. Chem. Educ. XXXX, XXX, XXX−XXX
Journal of Chemical Education
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HAZARDS Safety goggles must be worn at all times during the experiment. NiCl2·6H2O, triphenylphosphine, and chloroform-d are harmful if swallowed or inhaled, and can cause skin and eye irritation. Tricyclohexylphosphine, potassium phosphate, 4(trifluoromethyl)biphenyl, bis(triphenylphosphine)nickel(II) chloride, and 1,2-bis(diphenylphosphino)ethanenickel(II) chloride are irritants, and can cause skin and eye irritation. Phenylboronic acid is toxic, and is harmful if swallowed. Ethanol, t-amyl alcohol, and 1-bromo-4-(trifluoromethyl)benzene are flammable liquids, and can cause skin and eye irritation. No hazardous classification is determined for 1,2bis(diphenylphosphino)ethane and bis(tricyclohexylphosphine)nickel(II) chloride.
desired product, the percent conversions varied greatly among the catalysts employed. Not surprisingly, NiCl2·6H2O exhibited the lowest reactivity, where only 4% of the substrate converted (0.4 TON). NiCl2(PCy3)2 (20−28% conversion, 2−2.8 TON) was generally more reactive than NiCl2(PPh3)2 (11−19% conversion, 1.1−1.9 TON) due to the presence of the electrondonating PCy3 ligand. NiCl2(DPPE) was proven to be the most reactive catalyst, where 66−94% conversion of the product was obtained (6.6−9.4 TON). Due to the chelating effect, the incorporation of the bidentate DPPE ligand enhances the stability of the nickel(II) compound, and the intermediates generated in the catalytic cycle, which ultimately led to the increase in the reactivity of this catalyst.23 All of the groups of students were able to successfully complete the experiment by obtaining the desired dichlorophosphinenickel(II) products and conducting the catalytic Suzuki cross-coupling reactions. The percent yield of the prepared catalysts, the percent conversion of 4(trifluoromethyl)biphenyl, and the TON of catalysts varied by the type of the catalysts and the students’ skills. The students were able to correctly address the pedagogical goals mentioned previously in their lab reports. The students correctly determined the percent conversion and the TON in the catalysis run using the 19F{1H} NMR spectroscopy technique, and they were able to rationalize and draw a conclusion on the effect of the phosphine ligands on the formation and the reactivity of the catalysts.
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RESULTS AND DISCUSSION The experiment was performed by nine groups of two students from two sections of Inorganic Chemistry I (CHEM 280) laboratory. Each group was assigned to synthesize and perform a catalysis run of one dichlorophosphinenickel(II) catalyst, and shared the result with two other groups. The reference catalysis run of NiCl2·6H2O catalyst was performed separately by the instructor. A prelab problem set was assigned prior to the beginning of the experiment, which allowed the students to determine the quantity of reagents needed as well as the predicted 19 F NMR chemical shifts of 1-bromo-4(trifluoromethyl)benzene and 4-(trifluoromethyl)biphenyl from SciFinder. After the addition of NiCl2·6H2O and the phosphine precursor, NiCl2(PCy3)2 and NiCl2(DPPE) were produced instantly, while NiCl2(PPh3)2 was formed 15 min after the addition. The change in colors [green for NiCl2(PPh3)2,18 pink for NiCl2(PCy3)2,19 and orange for NiCl2(DPPE);20 see Supporting Information S14] as well as the precipitation of the products indicated the progress of the reactions. The rate of the formation of these catalysts depends greatly upon the electron-donating ability of the phosphine ligands. The electron-rich PCy3 facilitates the formation of the product, while the reaction is inhibited by the presence of the electronpoor PPh3.21 The bidentate DPPE ligand, however, promotes the formation of the product through the chelating effect.22 The percent yields of NiCl 2 (PPh 3 ) 2 , NiCl 2 (PCy 3 ) 2 , and NiCl2(DPPE) were in the ranges 40−55%, 47−84%, and 83−93%, respectively. The synthesized nickel products were characterized by UV−vis spectroscopy in CH2Cl2, where the λmax values of 407, 396, and 461 nm were observed for NiCl2(PPh3)2, NiCl2(PCy3)2, and NiCl2(DPPE), respectively. The observed λmax values of the synthesized nickel compounds were identical to those of the standard compounds. The UV− vis spectra of the synthesized and the standard nickel compounds are presented in Supporting Information S15−S17. The catalyzed Suzuki cross-coupling reactions were carried out with 10 mol % of the synthesized nickel(II) compound. The 19F{1H} NMR spectra of the final reaction mixture consisted of 2 sharp singlets (see Supporting Information S18− S23). The upfield signal corresponded to the unreacted 1bromo-4-(trifluoromethyl)benzene, which appeared at δ = −63.0 ppm. The downfield signal positioned at δ = −62.7 ppm belonged to the desired product, 4-(trifluoromethyl)biphenyl. The results from this 19F{1H} NMR spectroscopy indicated a highly selective conversion from the substrate to the desired biphenyl product. Although all of the catalysts produced the
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CONCLUSION This experiment introduces the concept of air-free synthesis of coordination compounds and their catalytic activity in a Suzuki cross-coupling reaction. The experiment was straightforward and suitable for an introductory or an intermediate level inorganic chemistry. The experiment exposed the students to the concept of an air-free synthesis and a metal-catalyzed homogeneous catalysis for first time in their undergraduate career. The experiment allowed the students to utilize 19F{1H} NMR spectroscopy as a novel technique for the product quantification from the catalytic reactions. The students were also able to determine the effect of the phosphine ligands toward the reactivity of the catalysts.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available on the ACS Publications website at DOI: 10.1021/acs.jchemed.6b00273. Complete list of chemicals and glassware, student handout, additional notes for the instructors, pictures for the setup of the air-free apparatus and of the synthesized nickel products, and UV−vis and NMR spectra (PDF, DOCX)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Todsapon Thananatthanachon: 0000-0002-2143-3337 Notes
The authors declare no competing financial interest. C
DOI: 10.1021/acs.jchemed.6b00273 J. Chem. Educ. XXXX, XXX, XXX−XXX
Journal of Chemical Education
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Catalysts: A Two-Part Experiment for Inorganic Chemistry. J. Chem. Educ. 2015, 92 (2), 378−781. (16) Hie, L.; Chang, J. J.; Garg, N. K. Nickel-Catalyzed SuzukiMiyaura Cross-Coupling in a Green Alcohol Solvent for an Undergraduate Organic Chemistry Laboratory. J. Chem. Educ. 2015, 92 (3), 571−574. (17) Girolami, G. S.; Rauchfuss, T. B.; Angelici, R. J. Synthesis of (C6H5)2PCH2CH2P(C6H5)2 in Liquid Ammonia. In Synthesis and Technique in Inorganic Chemistry; University Science Books: Sausalito, CA, 1999; pp 85−92. (18) Mboyi, C. D.; Gaillard, S.; Mabaye, M. D.; Pannetier, N.; Renaud, J. L. Straightforward Synthesis of Substituted Dibenzyl Derivatives. Tetrahedron 2013, 69 (24), 4875−4882. (19) Quasdorf, K. W.; Tian, X.; Garg, N. K. Cross-Coupling Reactions of Aryl Pivalates with Boronic Acids. J. Am. Chem. Soc. 2008, 130 (44), 14422−14423. (20) Van Hecke, G. R.; Horrocks, W. D., Jr. Ditertiary Phosphines Complexes with Nickel. Spectral, Magnetic, and Proton Resonance Studies. A Planar-Tetrahedral Equilibrium. Inorg. Chem. 1966, 5 (11), 1968−1974. (21) Birbeck, J. M.; Haynes, A.; Adams, H.; Damoense, L.; Otto, S. Ligand Effects on Reactivity of Cobalt Acyl Complexes. ACS Catal. 2012, 2 (12), 2512−2523. (22) Dutta, D. K.; Deb, B.; Hua, G.; Woollins, J. D. Chelate and Trans Effect of P,O Donor Phosphine Ligands on Rhodium Catalyzed Carbonylation of Methanol. J. Mol. Catal. A: Chem. 2012, 353−354, 7−12. (23) Chinchilla, R.; Najera, C. Recent Advances in Sonogashira Reactions. Chem. Soc. Rev. 2011, 40, 5084−5121.
ACKNOWLEDGMENTS The authors thank the Inorganic Chemistry I (CHEM 280) students at the University of Evansville, who provided the class data. The funding support from the chemistry department and the University of Evansville is gratefully acknowledged.
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REFERENCES
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DOI: 10.1021/acs.jchemed.6b00273 J. Chem. Educ. XXXX, XXX, XXX−XXX
