A Practical Modification of the Rosenmund Reduction

Wagner, Daniel; Gurien, Harvey; Rachlin, A. I.

doi:10.1111/j.1749-6632.1970.tb34976.x

Cited by 8 publications

(2 citation statements)

References 3 publications

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“…Use of a Pd/C catalyst combined with HCl scavengers (hindered secondary amines) and mild catalyst deactivators (thioanisole) produced N-protected piperidine carboxaldehyde for secretagogue MK-677 (of Merck) synthesis with an excellent yield in kilogram scale experiments . Siegel et al published a review about the Rosenmund processes used in the pharmaceutical production, among others about how 3,4,5-trimethoxy-benzaldehyde was prepared similarly but with Na-acetate as an HCl scavenger …”

Section: Resultsmentioning

confidence: 99%

“…13 Siegel et al published a review about the Rosenmund processes used in the pharmaceutical production, 14 among others about how 3,4,5-trimethoxy-benzaldehyde was prepared similarly but with Na-acetate as an HCl scavenger. 15 The application and investigation of bimetallic catalysts was a popular topic in the 1970s. A Pd−Cu/C catalyst proved to be highly efficient in the selective CC hydrogenation of a tetracycline derivative, without hydrogenolysis of an OH group, so it was also tested in acid chloride hydrogenations.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Overcoming Problems at Elaboration and Scale-up of Liquid-Phase Pd/C Mediated Catalytic Hydrogenations in Pharmaceutical Production

Tungler

Szabados

2016

Org. Process Res. Dev.

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The practical solutions for scale-up and production of intermediates or precursors of pharmaceuticals by liquidphase Pd/C mediated hydrogenation can be of considerable interest and deserve broader attention even if they have not been the focus of previously published research due to regulations of patent law. The practical obstacles are persistent and have been known for a long time, but for the most part remained unpublished. The most important discoveries and solutions that contributed to the successful scale-up of hydrogenations for pharmaceutical production were the following: (i) the poisoning of Pd/C catalyst with Fe 2+ ions for the selective hydrogenation of 2,6-dimethyl-1-nitrosopiperidine to the corresponding hydrazo compound; (ii) alloying of the deposited Pd metal with Cu for converting the aromatic acid chlorides into the corresponding aldehydes; (iii) alteration of the pH of the reaction mixture to basic values which enhanced the stereoselectivity of paracetamol hydrogenation; (iv) a useful modification of the catalyst preparation process, i.e., the acidification of the catalyst resulted in the hydrogenolysis of benzylic OH in a molecule containing a basic N atom; (v) use of two liquid phases, altogether a four-phase system, which permitted the hydrogenolysis of the S−S bond in a potential catalyst poisoning molecule; (vi) the preservation of the metallic Pd surface of the catalyst by saturation of the reaction mixture with hydrogen, resulting in a high H 2 /substrate ratio, increased the aldehyde yield in the hydrogenation of 4-chloro-butyric-acid-chloride by avoiding the unwanted poisoning effect of the hydrochloric acid. In the present article, these problems and their solutions, as they emerged during the scale-up of the processes, will be discussed in detail.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Overcoming Problems at Elaboration and Scale-up of Liquid-Phase Pd/C Mediated Catalytic Hydrogenations in Pharmaceutical Production

Tungler

Szabados

2016

Org. Process Res. Dev.

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Palladium on Barium Sulfate

Siegel

King

Shinkai

2001

Encyclopedia of Reagents for Organic Synthesis

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Aldehydes from Acid Chlorides by Modified R osenmund Reduction: 3,4,5‐Trimethoxybenzaldehyde

2003

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Aldehydes from acid chlorides by modified Rosenmund reduction: 3,4,5‐trimethoxybenzaldehyde product: 3,4,5‐trimethoxybenzaldehyde product: 3,4‐dimethylbenzaldehyde product: 3‐benzyloxy‐4,5‐dimethoxybenzaldehyde product: 3‐methoxy‐4‐nitrobenzaldehyde

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A Practical Modification of the Rosenmund Reduction

Cited by 8 publications

References 3 publications

Overcoming Problems at Elaboration and Scale-up of Liquid-Phase Pd/C Mediated Catalytic Hydrogenations in Pharmaceutical Production

Overcoming Problems at Elaboration and Scale-up of Liquid-Phase Pd/C Mediated Catalytic Hydrogenations in Pharmaceutical Production

Palladium on Barium Sulfate

Aldehydes from Acid Chlorides by Modified R osenmund Reduction: 3,4,5‐Trimethoxybenzaldehyde

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