Supporting Information
Potassium Isopropyl Xanthate (PIX): An Ultra-Efficient Palladium Scavenger
Hong Ren*, Christopher A. Strulson, Guy Humphrey, Rong Xiang, Guangtao Li,
Donald R. Gauthier, Kevin M. Maloney*
Typical Procedure for Palladium removal with PIX: Ceftolozane-TFA (14.3 g at 56 wt%) and
48 mL of a 2.5:1:2 water:DMAc:acetonitrile v:v:v (50:19:31 w/w) were combined and stirred at
22 °C to give a slurry. Isopropylxanthic acid potassium salt (PIX) (0.104 g, 5 mol%) was added
in one portion and the resulting reaction slurry was stirred at 22 °C for 30 min. A second portion
of isopropylxanthic acid potassium salt (0.104 g, 5 mol%) was added and the reaction mixture
was stirred at 22 °C for 30 min. Iodine (0.076 g, 2.5 mol%) was then added and the reaction
slurry was stirred at 22 °C for 1 h. The slurry was then filtered and the resulting waste cake was
washed with 8 mL of a 2.5:1:2 water: DMAc: acetonitrile. The filtrate and wash were combined
and cooled to 15 °C. Ammonium bisulfate (ammonium hydrogen sulfate) (1.449 g, 1.05 equiv)
was added and stirred at 15 °C for 15 min. Acetonitrile (12 mL) was added, followed by
Ceftolozane Sulfate DMAc solvate (0.08 g). The resulting slurry was aged at 15 °C for 3 h.
Acetonitrile (100 mL) was then charged over 10 h and the resulting slurry was aged at 15 °C for
1 h. Solids were filtered, washed with water:DMAc:acetonitrile (2.5:1:13) followed by
acetonitrile, and then dried under vacuum with a nitrogen sweep at 25 °C for 17 h to afford
Ceftolozane Sulfate DMAc solvate (9.51 g, 89% yield).
Typical Procedure for the preparation of PIX and derivatives: Charge isopropyl alcohol
(105g, 1750 mmol, 35 equiv) to reactor and begin cooling to 0 °C. Charge potassium tert-
butoxide (6.17 g, 55 mmol, 1.1 equiv) to reactor and stir the mixture for 10 minute at 0°C. Adjust
batch temperature to 22-25 °C and age batch for 2 hours. Charge PIX (0.5 g) seed to still. Age
batch for 15 minutes at 20-25°C and verify presence of seed bed. Charge CS
2
(3.81 g, 50 mmol,
1 equiv) in 2 hours. Age batch for 2 hours at 22-25 °C after addition of CS
2
is complete. Filter
batch. Charge 10X (by volume) isopropyl alcohol to crystallizer, transfer to filter, and
displacement wash through cake. Dry cake under vacuum at 22°C. Collected light yellow PIX
solid, (7.56 g, 87% yield).
Typical Procedure for Palladium Removal with Activated Carbons and Specialty Resins:
Ceftolozane-TFA (2.8 g at 56 wt%) and 9.6 mL of a 2.5:1:2 water:DMAc:acetonitrile v:v:v
(50:19:31 w/w) were combined and stirred at 22 °C to give a slurry. Activated carbon or
specialty resin (0.14 g, 5 wt%) was added in one portion and the resulting reaction slurry was
stirred at 22 °C for 30 min. The slurry was then filtered and the resulting waste cake was washed
with 8 mL of a 2.5:1:2 water: DMAc: acetonitrile. The filtrate and wash were combined and
cooled to 15 °C. Ammonium bisulfate (ammonium hydrogen sulfate) (0.29 g, 1.05 equiv) was
added and stirred at 15 °C for 15 min. Acetonitrile (0.25 mL) was added, followed by
Ceftolozane Sulfate DMAc solvate (0.016 g). The resulting slurry was aged at 15 °C for 3 h.
Electronic Supplementary Material (ESI) for Green Chemistry.
This journal is © The Royal Society of Chemistry 2017