42036-65-7Relevant articles and documents
Continuous-Flow Synthesis of Tramadol from Cyclohexanone
Monos, Timothy M.,Jaworski, Jonathan N.,Stephens, John C.,Jamison, Timothy F.
supporting information, p. 1888 - 1893 (2020/11/24)
A multioperation, continuous-flow platform for the synthesis of tramadol, ranging from gram to decagram quantities, is described. The platform is segmented into two halves allowing for a single operator to modulate between preparation of the intermediate by Mannich addition or complete the fully concatenated synthesis. All purification operations are incorporated in-line for the Mannich reaction. 'Flash' reactivity between meta-methoxyphenyl magnesium bromide and the Mannich product was controlled with a static helical mixer and tested with a combination of flow and batch-based and factorial evaluations. These efforts culminated in a rapid production rate of tramadol (13.7 g°h -1) sustained over 56 reactor volumes. A comparison of process metrics including E-Factor, production rate, and space-time yield are used to contextualize the developed platform with respect to established engineering and synthetic methods for making tramadol.
Microwave-assisted regioselective synthesis of β-aminoketones via the Mannich reaction
Gadhwal,Baruah,Prajapati,Sandhu
, p. 341 - 342 (2007/10/03)
A new and efficient method for the regioselective synthesis of β- aminoketones has been achieved by a simple reaction of formaldehyde, a secondary amine and a ketone under microwave irradiation.
Evaluation of some Mannich bases of cycloalkanones and related compounds for cytotoxic activity
Dimmock, JR,Sidhu, KK,Chen, M,Reid, RS,Allen, TM,et al.
, p. 313 - 322 (2007/10/02)
A number of Mannich bases of cycloalkanones and related quaternary ammonium compounds were prepared for cytotoxic evaluation in order to examine the theory that sequential release of alkylating agents produces increased bioactivity compared to related compounds containing only 1 potential alkylating site.Many of the compounds had significant activity against murine L1210 cells and various human tumours.Some correlations between structure and activity were noted but the biological data did not support the view that potential sequential liberation of cytotoxic species produced compounds with increased potency.The formation of various oximes and oxime benzoates as candidate prodrugs was achieved but in general these compounds were not cytotoxic at the concentrations utilized.This observation may be due to the fact that the oximes were much more stable in deuterated phosphate buffered saline over a period of 48 h at 37 deg than the Mannich bases, as revealed by 1H-NMR spectroscopy. Mannich bases / cytotoxic evaluations / prodrugs / 1H-NMR spectroscopy / structure-activity relationships
