ABSTRACT: Isolation of heat-sensitive reaction products in post-synthesis workup procedures often requires ambient- or lowtemperature solvent removal. In the method demonstrated here, solvent evaporation is driven by the pressure gradient between a distillation flask and a chilled receiver in an evacuated closed system containing a minimal amount of residual noncondensable gas. Using an all-glass apparatus, the method is exemplified by evaporation of solvent samples from a distillation flask containing 50 mL of either dimethylformamide,dimethylsulfoxide(DMSO), or N-methylpyrrolidone (NMP). The distillation flask is suspended in a water bath at temperatures of 18−28 °C, the evaporated solvent is collected in a receiver chilled with liquid nitrogen, and the entire process is completed in 90−140 min. The practicality of this method is further illustrated on a bench-chemistry scale by DMSO and NMP solvent removal from solutions of benzophenone, monitored by gravimetric and 1H NMR methods. Modification of the demonstrated method to mimic freeze-drying conditions (by reducing heat flow to the distillation flask) can be used for recovery of water-soluble compounds including polymers and biopolymers. We propose the name “cryovap” for this solvent removal method.
■ CONCLUSIONS
Solution-phase synthesis workup procedures dealing with isolation of heat-sensitive products may benefit from the ambient- or low-temperature solvent removal method described in this paper. The distillation in this process is driven by the pressure gradient between a distillation flask and a receiver in an evacuated closed system containing a minimal amount of residual noncondensable gas. In principle, the described method is analogous to molecular distillation but with a greatly increased mean free path of a molecule of the distillate vapor. The method’s versatility is exemplified by distillation of dimethylformamide,dimethyl sulfoxide, and N-methylpyrrolidone; 50 mL of each was evaporated at 18−28 °C over the course of 90−140 min when liquid nitrogen was used as a cryogen. The practicality of the method was further demonstrated by the distillation of water at 21 °C into an ice-chilled receiver, which can be useful for both smaller- and larger-scale processes. The utility of the described method is also exemplified by DMSO and NMP solvent removal from solutions of benzophenone, monitored by gravimetric and 1H NMR methods. Finally, a slight modification of the demonstrated method to yield freezedrying conditions (by reducing heat flow to the distillation flask)
was shown to be applicable for recovery of water-soluble polymers. The procedure is performed in an all-glass apparatus and can therefore be used for the removal of volatile corrosive liquids, including halogenating and acylating agents, solutions of hydrogen halides, and other volatile acids, with minimal risk of equipment damage. This method is recommended for general organic, biological, organometallic, and coordination chemistry solution-phase synthesis routines on a basic or applied research and development scale. Due to the key role the cryogen plays in driving the evaporation of the solvent in the procedure, we propose to name this solvent removal method “cryovap.”
■ EXPERIMENTAL SECTION
Example 1. A 200 mL pear-shaped Schlenk flask was charged with a 10mmstir bar, 50 mL of DMSO, and 0.5 mL of isooctane.The receiver of the apparatus was charged with 0.5 mL of isooctane, carefully greased, and attached to the Schlenk flask containing DMSO. As the Schlenk flask was held over a working magnetic stirrer, the apparatus was evacuated for 2−3 min. During pumping, the isooctane evaporated and its vapor expelled the residual air within the apparatus. The stopcock was closed, and the system was disconnected from the vacuum line and arranged as shown in Figure 4. The water bath was filledwith water and prewarmed to 28 °C (to supply thermal energyfor evaporation and to prevent the DMSO from freezing), and the magnetic stirrer was set at high rpm. After about 5 min of stirring, the temperature between the water bath and the solvent was assumed to reach equilibrium. A Dewar flask charged with liquid nitrogen (about one-third of its volume) was adjusted to a position so that only the bottom of the receiver was submerged in the cryogen. Over the course of evaporation, the water bath temperature was maintained between 27 and 28 °C, and the receiver was gradually immersed deeper into the Dewar flask.The solvent in the distillation flask remained liquid at all times,and the distillation was complete in 105 min.
■ AUTHOR INFORMATION
Corresponding Authors
Igor V. Kolesnichenko − Sandia National Laboratories,
Albuquerque, New Mexico; Email: ikolesn@sandia.gov
Galina Z. Goloverda − Xavier University, New Orleans,
Louisiana; Email: gzgolove@xula.edu
Vladimir L. Kolesnichenko − Xavier University, New
Orleans, Louisiana; Email: vkolesni@xula.edu
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.oprd.9b00368
https://dx.doi.org/10.1021/acs.oprd.9b00368
Org. Process Res. Dev. XXXX, XXX, XXX−XXX
