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Synthesis 2012; 44(15): 2469-2473
DOI: 10.1055/s-0032-1316550
DOI: 10.1055/s-0032-1316550
paper
Reductive Amination by Continuous-Flow Hydrogenation: Direct and Scalable Synthesis of a Benzylpiperazine
Further Information
Publication History
Received: 19 March 2012
Accepted after revision: 18 May 2012
Publication Date:
02 July 2012 (online)
Abstract
A benzylpiperazine was prepared directly from the corresponding benzaldehyde and piperazine on a continuous-flow hydrogenation apparatus. The synthesis was protecting group free, safe, and environmentally friendly. Large-scale synthesis under flow hydrogenation conditions was also demonstrated.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synthesis.
- Supporting Information
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References
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- 12 The price difference is on a per mole basis. From the same vendor (Sigma-Aldrich), N-Boc piperazine costs $335/25 g, or $2500/mol; piperazine costs $16/100 g, or $14/mol at the time the manuscript was written
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- 14 Reactions were conducted using a commercially available instrument, the H-Cube (manufactured by ThalesNano Nanotechnology Inc. in Budapest, Hungary)
- 15 A preliminary NMR experiment was performed to monitor formation of intermediate (s). Equal molar of 2 and piperazine were dissolved in CD3OD and allowed to stand at r.t. for 48 h. 1H NMR showed mainly three compounds in the ratio of 1:1:0.2. The structures were tentatively assigned to aldehyde 2, piperazine hemiaminal methyl ether, and dimethyl ketal, respectively
- 16 Cartridges for H-Cube and H-Cube Midi contain catalyst of different particle sizes. The actual difference varies based on the nature of catalyst and the batches. For an excellent analysis of various parameters that can impact cartridge performances, see: Bryan MC, Wernick D, Hein CD, Petersen JV, Eschelbach JW, Doherty EM. Beilstein J. Org. Chem. 2011; 7: 1141
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For select examples, see:
For select examples of flow-hydrogenation applications, see: