In the Laboratory
Formation of a Ruthenium–Arene Complex, Cyclometallation with a Substituted Benzylamine, and Insertion of an Alkyne
W
Synthetic Experiments in Organometallic Chemistry Michael J. Chetcuti and Vincent Ritleng* Laboratoire de Chimie Organométallique Appliquée, UMR CNRS 7509, Ecole Européenne de Chimie, Polymères et Matériaux, Université Louis Pasteur, 25 rue Becquerel, 67087 Strasbourg, France; *
[email protected] The activation of carbon–hydrogen bonds (known as C⫺H activation) is an important reaction in chemistry and in catalysis. Both inter- (1) and intramolecular (2) C⫺H activation reactions are known, but it has long been recognized that intramolecular activation is much easier as the C⫺H bond is held close to the metal center by chemical bonds and thus the reaction becomes favored entropically (2n). As intramolecular C⫺H activation reactions create a new metallacycle, these reactions are known as cyclometallation reactions. The cyclometallated products have a new metal–carbon bond. When the C⫺H group of a ligand-bound phenyl group cyclometallates, it is usually the ortho C⫺H bond that is involved, so these reactions are often called orthometallations. An early example is shown in Scheme I (3). Chemists have taken advantage of this reaction to functionalize C⫺H bonds by coupling the activated intermediates with unsaturated substrates, thus forming new C⫺C bonds and achieving atom economy (4). A well-known example is the ruthenium-catalyzed addition of C⫺H bonds at the ortho-position of aromatic ketones to olefins developed by Murai and co-workers (Scheme II) (5).
Scheme I. Cyclometallation of one PPh3 ligand of [IrCl(PPh3)3].
Scheme II. Murai’s coupling of aromatic ketones to olefins.
1014
Journal of Chemical Education
•
The three-step synthesis presented here allows the functionalization of an aromatic amine by forming new C⫺C and C⫺N bonds via an intramolecular C⫺H activation under mild conditions. The reactions are stoichiometric and allow the students to isolate the different organometallic intermediates and, therefore, to have a better understanding of the global reaction pathway. These experiments have been successfully performed by students in the second year of a joint masters degree in chemistry and chemical engineering. Nevertheless, they are relatively simple synthetically and advanced undergraduates are certainly capable of preparing these complexes following the procedures described here. No specialized techniques or equipment are required apart from access to a nitrogen manifold and a vacuum pump. Experiment Overview Each step in this three-step synthesis is of pedagogic interest. The first reaction, the formation of [Ru(η6-C6H6)(µCl)Cl]2 1, demonstrates the preparation of an arene complex by reduction of a Ru(III) complex with ethanol and 1,3cyclohexadiene (Scheme III) (6). The driving force for this reaction is the aromatization of 1,3-cyclohexadiene and its ligation to the ruthenium atom. The Ru(II) is complexed to the arene via the interaction of the benzene π molecular orbitals with the set of ruthenium 4d orbitals. The second reaction involves the cyclometallation of N,N-dimethylbenzylamine by the ruthenium–arene complex 1 (7). The reaction likely proceeds via loss of one chloride ion and the formation of a cationic ruthenium complex A that is stabilized both by ligation by the remaining chloride ion and by solvation by polar acetonitrile ligands. The substituted benzylamine presumably coordinates to the ruthenium through the nitrogen atom, giving B. The ortho C⫺H group then undergoes a base-assisted cyclometallation to the ruthenium atom, whose mechanism is believed to be akin to an aromatic electrophilic substitution (Scheme IV) (7). Note that the large ruthenium cationic complex is better stabilized
Scheme III. Preparation of [Ru(η6-C6H6)(µ-Cl)Cl]2.
Vol. 84 No. 6 June 2007
•
www.JCE.DivCHED.org
In the Laboratory
in the solid state by the large and non-coordinating PF6− anion. It is well known that salts with comparable cation and anion sizes have higher lattice energies (8). The yellow product 2 is purified by passing the reaction mixture through a short alumina column and is crystallized from an acetonitrile兾diethylether mixture. A 1H NMR spectrum of this complex in CD3CN is quite informative. The molecule has no symmetry (it belongs to the point group C1). Nevertheless, rapid rotation of the benzene ring about the ruthenium–ring-centroid axis renders all six aromatic protons of the ligand equivalent on the 1H NMR timescale, thus a single signal is seen for these protons. None of the other protons are chemically equivalent so the cyclometallated ring protons appear as an ABCX multiplet system with the ortho proton being significantly deshielded. The methylene group protons are observed as an AB doublet of doublets. Two distinct singlets are seen for the two sets of NMe2 protons, and another signal is observed for the coordinated CH3CN signal that undergoes rapid exchange with the solvent. The information gleaned from the 1H NMR spectrum is informative and in complete agreement with the structure of a closely related complex (9). The third reaction is the insertion of diphenylacetylene into the metallacycle 2. This reaction proceeds relatively rapidly and the reaction is over in four hours (8). Diphenylacetylene inserts into the ruthenium–carbon bond of the five-membered metallacycle ring leading to a new seven-membered ruthenacycle C (10), which subsequently undergoes a reductive C⫺N coupling leading to the final complex 3 (Scheme V). The formation of new C⫺C and C⫺N bonds shows the activating effect of the ruthenium atom in the cyclometallated product. It should be pointed out to the students that the intermediate seven-membered metallacycle can be isolated when acetylenes substituted by electron withdrawing groups are used (10). It should also be mentioned that all the ruthenium complexes prepared observe the 18-electron rule.
The yellow product 3 is purified by crystallization from a chloroform兾diethylether mixture and analyzed by 1H NMR in CDCl3. As in its precursor 2, the six aromatic protons of the benzene ring of 3 are observed as a singlet, and none of the other protons are chemically equivalent. Thus, the methylene group protons are still observed as an AB spin system, and the NMe2 protons are still seen as two distinct singlets. The assignment of the aromatic protons is less clear owing to partial overlap of the phenyl and C6H4 protons,
Scheme IV. Cyclometallation mechanism of N,N -dimethylbenzylamine by complex 1.
Scheme V. C–C and C–N bond formation by reaction of diphenylacetylene with complex 2.
www.JCE.DivCHED.org
•
Vol. 84 No. 6 June 2007
•
Journal of Chemical Education
1015
In the Laboratory
but the signals integrate for 14 protons as expected. However, the C6H4 protons can readily be assigned if a non-aromatic alkyne, such as 3-hexyne for example, is used instead of diphenylacetylene (9). Summary of Procedure The reactions are appropriate for an advanced undergraduate inorganic laboratory class or for a graduate class. The experiments proceed in high yield and reproducibility. While ruthenium (as the hydrated chloride salt) is not inexpensive (it can be purchased from Strem Chemicals at 25 g for EUR 243, that is, approx $300 at current market prices), it is by far the least expensive of the noble metals and the reaction need only be done on a 1.00 g scale. If time is of the essence, the first step can be bypassed by purchasing the commercially available benzene ruthenium dichloride dimer. The latter species can also be prepared by the instructor well in advance and any surplus stored until the experiment is performed again, since this complex does not degrade when kept in a sealed container. Organic reagents are all commercially available. The reaction sequence requires three laboratory sessions of approximately one day each to be completed. We recommend that each step be done during one laboratory session. Complex 1 can be stored in a closed vial in air to the next session, and product 2 is best kept in a Schlenk tube under nitrogen. The first reaction is carried out in air and the products of the other two reactions are readily accessible using a simple nitrogen atmosphere, without extraordinary precautions to remove oxygen. The solvents do not need to be distilled. The experiments show the need for manipulating complexes under nitrogen, but the reactions are forgiving and students are not unduly penalized if some air accidentally enters the system, as the products 2 and 3 are not highly air-sensitive. The yields of the first and third reactions are close to quantitative, and the yield of the cyclometallated product, following passage through an alumina column and recrystallization, is respectable (ca. 50%). The filtration on alumina necessary to obtain 2 provides an introduction to chromatography under a protective atmosphere. Purification of products 2 and 3 by recrystallization provides a good example of how impurities can be removed to obtain a product of high purity. The series of experiments presented here is instructive as it clearly shows how a transition-metal organometallic compound can activate a relatively unreactive C⫺H bond. The cyclometallated complex is reactive and is then used to effect C⫺C and C⫺N coupling reactions that would otherwise not take place. Students appreciate that the C⫺C and C⫺N bond formation reactions do not take place in the absence of the transition-metal organometallic complex. It is pointed out to students that this activation effect on otherwise unreactive bonds is a major reason that organometallic complexes are used in homogeneous catalysis. The students are also gratified that the 1H NMR spectra of the complexes are interpretable and are in agreement with the proposed structures. We believe that the relative dearth of modern synthetic organometallic reactions suitable for teaching laboratories (see ref 11 for a recent example) makes this article a useful contribution to the literature.
1016
Journal of Chemical Education
•
Hazards Diethyl ether is extremely flammable and can form explosive peroxides. Methanol, ethanol, and acetonitrile are readily flammable solvents. Methanol is toxic in case of inhalation, skin contact and ingestion, and can cause irreversible damage. Chloroform is harmful with severe health risks in case of prolonged exposure by inhalation and ingestion. 1,3-Cyclohexadiene is readily flammable and has a disagreeable odor. N,N-dimethylbenzylamine is flammable and can cause burns. Sodium hydroxide and potassium hexafluorophosphate can cause severe burns. Alumina is an inhalation hazard owing to its small particle size. The ruthenium complexes have not been tested for toxicity and therefore should be handled with care. W
Supplemental Material
A student handout containing detailed experimental procedures; notes for the instructor including spectral data for all products; and 1H NMR spectra of 2 and 3 are available in this issue of JCE Online. Literature Cited 1. For reviews concerning intermolecular C⫺H activation reactions, see: (a) Parshall, G. W. Acc. Chem. Res. 1975, 8, 113. (b) Bergman, R. G. Science 1984, 223, 902. (c) Crabtree, R. H. Chem. Rev. 1985, 85, 245. (d) Arndtsen, B. A.; Bergman, R. G.; Mobley, T. A.; Peterson, T. H. Acc. Chem. Res. 1995, 28, 154. (e) Shilov, A. E.; Shul’pin, G. B. Chem. Rev. 1997, 97, 2879. 2. For reviews concerning intramolecular C⫺H activation reactions, see: (a) Parshall, G. W. Acc. Chem. Res. 1970, 3, 139. (b) Dehand, J.; Pfeffer, M. Coord. Chem. Rev. 1976, 18, 327. (c) Bruce, M. I. Angew. Chem., Int. Ed. 1977, 16, 73. (d) Webster, D. E. Adv. Organomet. Chem. 1977, 15, 147. (e) Omae, I. Chem. Rev. 1979, 79, 287. (f ) Omae, I. Coord. Chem. Rev. 1980, 32, 325. (g) Omae, I. Coord. Chem. Rev. 1982, 42, 245. (h) Constable, E. C. Polyhedron, 1984, 3, 1037. (i) Rothwell, I. P. Polyhedron 1985, 4, 177. (j) Rothwell, I. P. Acc. Chem. Res. 1988, 21, 153. (k) Omae, I. Coord. Chem. Rev. 1988, 83, 137. (l) Newkome, G. R.; Puckett, W. E.; Gupta, V. K.; Kiefer, G. E. Chem. Rev. 1986, 86, 451. (m) Ewans, D. W.; Baker, G. R.; Newkome, G. R. Coord. Chem. Rev. 1989, 93, 155. (n) Ryabov, A. D. Chem. Rev. 1990, 90, 403. (o) Canty, A. J.; van Koten, G. Acc. Chem. Res. 1995, 28, 406. 3. Bennett, M. A.; Milner, D. L. J. Am. Chem. Soc. 1969, 91, 6983. 4. Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731. 5. Murai, S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani, N. Nature 1993, 366, 529. 6. Zelonka, R. A.; Baird, M. C. Can. J. Chem. 1972, 50, 3063. 7. Fernandez, S.; Pfeffer, M.; Ritleng, V.; Sirlin, C. Organometallics 1999, 18, 2390. 8. See discussion of this topic in: Shriver, D. F.; Atkins, P. W. Inorganic Chemistry, 3rd ed.; Oxford University Press: Oxford, 1999; Chapter 2, pp 58–60. 9. Abbenhuis, H. C. L.; Pfeffer, M.; Sutter, J.-P.; de Cian, A.; Fischer, J.; Li Ji, H.; Nelson, J. H. Organometallics 1993, 12, 4464. 10. Pfeffer, M.; Sutter, J.-P.; Urriolabietia, E. P. Bull. Soc. Chim. Fr. 1997, 134, 947. 11. Taber, D. F.; Frankowski, K. J. J. Chem. Educ. 2006, 83, 283.
Vol. 84 No. 6 June 2007
•
www.JCE.DivCHED.org
