Direct Synthesis of Secondary Amines From Alcohols and Ammonia Catalyzed by a Ruthenium Pincer Complex
- 3.4k Downloads
Efficient and selective direct synthesis of secondary amines from primary alcohols and ammonia with liberation of water has been achieved, with high turnover numbers and with no generation of waste. In case of benzylic alcohols, imines rather than amines are obtained. This atom economical, environmentally benign reaction is homogenously catalyzed by a well-defined bipyridine based Ru(II)-PNN pincer complex.
KeywordsAlcohol Secondary amine Ammonia Ru-pincer complex Homogenous catalysis
Amines and their derivatives are a very important class of compounds in chemistry and biology. They are highly versatile building blocks for various organic synthetic targets and are used as dyes, color pigments, electrolytes, agricultural chemicals, herbicides, polymers, and functionalized materials . In addition, they are essential pharmacophores in numerous biologically active compounds, and amine groups are present in vitamins, hormones, alkaloids, neurotransmitters, or natural toxics [2, 3]. Owing to their extensive applications, the development of versatile and efficient methods for the synthesis of secondary amines has attracted much interest in the area of catalysis. Because of the abundance and low price of ammonia, much attention has been focused on its use as a nitrogen source for organic synthesis [4, 5]. Recent reports on homogenous catalytic systems using ammonia as the substrate include palladium-catalyzed telomerization of butadiene and ammonia giving primary alkylamines , Pd-catalyzed allylic amination , copper- and palladium-catalyzed coupling reactions of ammonia with aryl halides to form arylamines [8, 9, 10], rhodium- and iridium-catalyzed reductive aminations of carbonyl compounds with ammonium formate and ammonia to afford primary alkylamines [11, 12, 13] and palladium-catalyzed arylation of ammonia to afford di- and triarylamines .
In the context of “green and sustainable chemistry” (GSC), the catalytic synthesis of amines from readily available alcohols using ammonia and generating no hazardous waste is of much current interest. In 2008, we reported the first direct homogenous catalytic selective amination of primary alcohols to primary amines using ammonia . Later, the research groups of Vogt  and Beller  developed methods for the conversion of secondary alcohols to primary amines with ammonia. Catalytic methods for the synthesis of secondary amines starting from alcohols and amines were described by Williams [17, 18], Yamaguchi [19, 20], Beller [21, 22], Yus [23, 24] and Kempe [25, 26]. Multi alkylation of ammonia to get either secondary or tertiary amines was developed by Yamaguchi, Fujita and co-workers using an iridium complex as catalyst [27, 28]. Herein, we report the selective synthesis of secondary amines from alcohols and ammonia with liberation of water, with considerable turnover numbers (up to ~500) and with no generation of waste.
Recently we found that the pre-catalyst 3 analogue of 2, efficiently catalyzes in the presence of catalytic base the dehydrogenative coupling of primary alcohols with secondary amines to form tertiary amides , and the direct catalytic olefination of alcohols using sulfones, with liberation of H2 . Herein we report the catalytic activity of the pre-catalyst 3 in bis-alkylation of ammonia with primary alcohols to get secondary amines, or imines (in the case of benzylic alcohols) selectively.
2 Results and Discussion
Direct synthesis of secondary amines (or imines) from primary alcohols and ammonia catalyzed by the ruthenium complex 3 and base, according to Scheme 1
34 + 14c
In summary, we have developed a new atom-economical, environmentally benign catalytic system for the direct synthesis of secondary amines from alcohols and ammonia. The reaction is homogenously catalyzed by the bipyridine-based Ru(II)-PNN pincer complex 3 in the presence of an equimolar amount of base (relative to Ru). The reactions of ammonia with aliphatic alcohols gave secondary amines exclusively, while those of aromatic alcohols afforded imines selectively. Only 0.2 mol% catalyst is needed. The efficiency, selectivity, atom-economy and mild reaction conditions of this process make it attractive for the selective synthesis of secondary amines or imines from readily available, renewable alcohols.
All experiments with metal complexes and phosphine ligands were carried out under N2 in a Vacuum Atmospheres glovebox equipped with a MO 40-2 inert gas purifier, or using standard Schlenk techniques. All non-deuterated solvents were refluxed over sodium/benzophenoneketyl and distilled under argon atmosphere. All solvents were degassed with argon and kept in the glove box over 4Å molecular sieves. CD2Cl2 was used as received. Most of the chemicals (alcohols) used in the catalytic reactions were purified according to standard procedures (vacuum distillation). GC analysis were carried out using a Carboxen 1000 column on a HP 690 series GC system or HP-5 cross linked 5 % phenylmethylsilicone column (30 m × 0.32 mm × 0.25 µm film thickness, FID) on a HP 6890 series GC system using m-xylene (1 mmol) as an internal standard.
4.1 Synthesis of RuHCl(CO)([BPy(Ph)PNN] (3)
The hydrido-chloride pincer complex 3 was prepared by a reaction of the ligand [BPy(Ph)PNN] with RuHCl(CO)(PPh3)3 according to a previously reported procedure from our group . Crystals suitable for a single-crystal X-ray diffraction study were obtained from a mixture of CD2Cl2: THF (20 mg in 0.4: 0.1 mL) at −32 °C after several days (~10 days).
4.2 X-ray Crystal Structure Determination of 3
A crystal was mounted in a MiTeGen loop and flash frozen in a nitrogen stream at 120 K. Data were collected on a Bruker Apex-II CCD diffractometer generator equipped with a sealed tube with MoKα radiation (λ = 0.71073 Å) and a graphite monochromator. The structure was solved using direct methods with AUTOSTRUCTURE module based on F 2 [48, 49].
Chemical Formula: 2(C24H20ClN2OPRu).C4H8O, Orange, plate, 0.10 × 0.10 × 0.01 mm3, monoclinic, C2/c, a = 29.1301(11) Å, b = 12.5264(4) Å, c = 13.5058(5) Å, β = 108.826(3) deg., V = 4664.6(3) Å3, Z = 4, fw = 1111.92, D c = 1.583 Mg/m3, μ = 0.880 mm−1. Full matrix least-squares of refinement based on F 2 gave an agreement factor R = 0.0323 for data with I > 2σ(I) and R = 0.0599 for all data (4757 reflections) with a goodness-of-fit of 1.006. Idealized hydrogen atoms were placed and refined in the riding mode, with the exception of the hydride ligand H1-Ru, which was located in the difference map and refined independently.
4.3 General Procedure for the Catalytic Direct Amination of Alcohols to Amines
Complex 3 (0.02 mmol), KO t Bu (0.02 mmol), an alcohol (10 mmol), and toluene (2 mL) were added to a 90 mL Fischer-Porter tube under an atmosphere of purified nitrogen in a Vacuum Atmospheres glovebox. The tube was taken out of the glovebox and was purged by three successive cycles of pressurization/venting with NH3 (20 psi), then pressurized with NH3 (7 atm). The solution was heated at 135 °C (bath temperature) with stirring for 48 h (Table 1). After cooling to room temperature, excess NH3 was vented off carefully and the products were analyzed by GC using m-xylene as an internal standard.
This research was supported by the European Research Council under the FP7 framework (ERC No. 246837) and by the Israel Science Foundation. D. M. holds the Israel Matz Professorial Chair of Organic Chemistry. E. B thanks to the CSIR-NCL (Start-up Grant No. MLP028726).
- 1.Lawrence SA (2005) Amines: synthesis, properties and applications. Cambridge University Press, CambridgeGoogle Scholar
- 2.Seewald N, Jakubke HD (2009) Peptides: chemistry and biology. Wiley, Weinheim, p 1Google Scholar
- 3.Hughes AB (ed.) (2009) Freeland in amino acids, peptides and proteins in organic chemistry. Vol. 1, Wiley, Weinheim, p 43Google Scholar
- 20.Yamaguchi R, Mingwen Z, Kawagoe S, Asai C, Fujita K (2009) Synthesis 1220Google Scholar
- 32.Gunanathan C, Milstein D (2011) Top Organomet Chem 37:55Google Scholar
- 33.Balaraman E, Milstein D (2014) Top Organomet Chem 48:14Google Scholar
- 48.Sheldrick GM (1997) SHELXS-97, Program for Crystal Structure Solution. University of Göttingen, GöttingenGoogle Scholar
- 49.Sheldrick GM (1997) SHELXL-97, Program for Crystal Structure Refinement. University of Göttingen, GöttingenGoogle Scholar