Preparation of cisplatin using microwave heating and continuous-flow processing as tools

Inorganic Chemistry Communications

Volumn 14, Issue 3, 2011, Pages 481-483

  Pedrick, Elizabeth A ^a   Leadbeater, Nicholas E ^a  

^a UNIVERSITY OF CONNECTICUT   (United States)

Author keywords

Cancer; Cisplatin; Flow chemistry; Microwave heating; Platinum chemistry; Water

Indexed keywords

EID: 79952143127     PISSN: 13877003     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.inoche.2011.01.005     Document Type: Article

References (22)

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14. For a review, see: G.L. Powell N.E. Leadbeater, Microwave Heating as a Tool for Sustainable Chemistry 2010 Taylor and Francis Boca Raton FL 175 205
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17. 2O): δ = -2104.0 ppm.
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19. 3 (2.08 mmol, 160 mg), KCl (2.68 mmol, 0.2 g) in water (2.5 mL). This tube was then sealed in the microwave unit. The reaction mixture, being stirred continuously, was heated using a maximum microwave power of 150 W to the target temperature of 100 °C and then held at this temperature for 15 min. The product mixture was then cooled to 60 °C, the tube was taken out of the microwave unit and allowed cool to room temperature before completing precipitation by placing in an ice bath. The precipitate was filtered and then washed with ice water. The mother liquor was concentrated by gently boiling off the excess water. It was washed with 0.1 M HCl. A second crop of 1 was obtained, the combined crops equating to an 82% yield.
20. For an overview see: Chemical Reactions and Processes under Flow Conditions S.V. Luis, E. Garcia-Verdugo, 2010 Royal Society of Chemistry Cambridge UK
21. M. Damm, T.N. Glasnov, and C.O. Kappe Org. Proc. Res. Dev. 14 2010 215
22. 3 (20.8 mmol, 1.6 g), KCl (26.8 mmol, 2.0 g) in water (50 mL). Using the Uniqsis FlowSyn, a 14 mL capacity PTFE coil reactor was put in place around the aluminium heating block. At the exit of the coil reactor, a 100 psi rate back-pressure regulator was attached and kept in close proximity to the heater block. A small length of PTFE tubing was attached to the exit of the back-pressure regulator, this being used to take product mixture from the heated zone to a 100 mL capacity collection vessel. The block was heated from room temperature to 100 °C, passing water through the coil reactor, from bottom to top, at a rate of 0.8 ml/mL. The flow was then changed from solvent (water) to reaction mixture by means of a switch on the control unit. The reaction mixture was then passed through the coil reactor at a rate of 0.8 mL/min. As the mixture neared the end of the coil reactor, an empty, clean collection vessel was put in place. After all the reaction mixture has entered the coil reactor, the flow was changed back to solvent and water flowed through the reactor at a rate of 0.8 mL/min to push the remaining reaction mixture through and out into the collection vessel. As soon as this was achieved, the flow was stopped so as to avoid dilution of the product mixture with water. The product mixture was then placed in ice to facilitate precipitation of cisplatin. This solution was then filtered giving a first crop of cisplatin in approximately 45% yield (648 mg). The mother liquor was then re-run through the flow reactor using the same protocol. Again the product solution was cooled and the precipitated cisplatin collected by filtration. The mother liquor was concentrated by gently boiling off most of the water. A small quantity of 0.1 M HCl was added and a second crop of 1 was obtained, the combined crops equating to a 72% yield.