Effective Conversion of Heteroaromatic Ketones into Primary Amines via Hydrogenation of Intermediate Ketoximes

Abstract

A process to access heteroaromatic primary amines from the corresponding heteroaromatic ketones has been developed. A broad range of previously reported methods to convert ketones to primary amines was examined on heterocyclic ketones without success, including Leuckart–Wallach conditions, borane reductions, and transition-metal-catalyzed hydrogenations. Unique among the catalysts examined, Raney cobalt produced the desired primary heterocyclic amine. Raney cobalt hydrogenation of structurally varied heterocyclic ketoximes was demonstrated to form primary amines in good selectivity under mild conditions, and the products are easily isolated in high yield. Additionally, this is the first report of a systematic evaluation of the capabilities of Raney cobalt as an oxime hydrogenation catalyst.

Key words

hydrogenation - Raney cobalt - heterogeneous catalysis - amines - reduction - heterocycles

• References and Notes

• 1a Nugent TC, El-Shazley M. Adv. Synth. Catal. 2010; 352: 753
• 1b LaRock RC. Comprehensive Organic Transformations, A Guide to Functional Group Preparations. Wiley; New York: 1999. 2nd ed
• 2a Abiraj K, Gowda DC. Synth. Commun. 2004; 34: 599
• 2b McEachern EJ, Yang W, Chen G, Skerlj RT, Bridger GJ. Synth. Commun. 2003; 33: 3497
• 2c Cai Z, Liu G, Jiao G, Senanayake CH, Tang W. Synthesis 2013; 45: 3355
• 2d Chu Y, Shan Z, Liu D, Sun N. J. Org. Chem. 2006; 71: 3998
• 2e Baruah B, Dutta MP, Boruah A, Prajapari D, Sandhu JS. Synlett 1999; 409
• 2f Itsuno S, Sakurai Y, Ito K. Synthesis 1988; 995
• 2g Abele S, Breitenmoser RA, Fink T. Org. Process Res. Dev. 2012; 2008
• 3a Cwiek R, Niedziejko P, Kaluza Z. J. Org. Chem. 2014; 79: 1222
• 3b Bourrain S, Showell GA. Synthesis 1994; 505
• 3c Spreitzer H, Buchbauer G, Pueringer C. Tetrahedron 1989; 45: 6999
• 3d Burkhard JA, Wuitschik G, Plancher JM, Rogers-Evans M, Carreira EM. Org. Lett. 2013; 15: 4312
• 4 Kitamura M, Lee D, Hayashi S, Tanaka S, Yoshimura M. J. Org. Chem. 2002; 8685
• 5a Abdel-Magid AF, Carson KG, Harris BD, Maryanoff CA, Shah RD. J. Org. Chem. 1996; 3849
• 5b Bharracharyya S, Miriyala B, Williamson JS. Tetrahedron 2004; 1463
• 5c Mattson RJ, Pham KM, Leuck DJ, Cowen KA. J. Org. Chem. 1990; 2552
• 6a Shan Z, Chu Y, Liu D, Sun N. J. Org. Chem. 2006; 3998
• 6b Burkhardt ER, Coleridge BM. Tetrahedron Lett. 2008; 5152
• 7a Adkins H, Winans CF. J. Am. Chem. Soc. 1933; 2051
• 7b Iffland DC, Yen TF. J. Am. Chem. Soc. 1954; 76: 4180
• 7c Ran L, Liang H, Guan Z. Chin. J. Org. Chem. 2013; 33: 66
• 8a Banwell MG, Jones MT, Reekie TA, Schwartz BD, Tan SH, White LV. Org. Biomol. Chem. 2014; 12: 7433
• 8b Gebauer-Henke E, Leitner W, Prokofieva A, Vogt H, Müller TE. Catal. Sci. Technol. 2012; 2: 2539
• 9 General Oxime Procedure: Ketone (76 mmol), hydroxylamine hydrochloride (83 mmol), NaOAc (83 mmol) and EtOH (140 mL) were combined and heated to reflux for 3 h. White solid (oxime) was observed to precipitate from the solution during this time. The mixture was then cooled, deionized H₂O (140 mL) was added, and the mixture was then stirred for 10 min. The solids were isolated by filtration, washed with H₂O (140 mL) and dried at r.t. under nitrogen flow on the filter.General Reduction Procedure: To a mixture of oxime (0.86 mmol) and Raney Co 2724 (200 mg, slurry in H₂O) were added THF (1.5 mL) and MeOH (1.5 mL). The reaction mixture was purged with nitrogen twice then pressurized to 60 psi H₂ at 50 °C. The reaction was deemed complete when H₂ consumption ceased, typically after 2–10 h. Upon completion, the reaction was filtered through a pad of celite and washed with MeOH. The filtrate was then concentrated under reduced pressure, and purified by flash chromatography (CH₂Cl₂–MeOH, 95:5) to furnish the title compound. Alternatively, the product was conveniently isolated in high purity as the HCl salt. After filtering off the catalyst, the filtrate solvent was changed to MTBE (1.5 mL) and HCl (0.95 mmol, 1 M in Et₂O) was added dropwise to crystallize the salt. The resulting HCl amine salt was then isolated by filtration and washed with MTBE.