Comparison of Spherical and Irregular Silicas in Flash Chromatography

Flash chromatography is an efficient, rapid and economical technique for the purification of organic compounds. Introduced over thirty years ago, it has gained popularity with the introduction of disposable pre-packed flash cartridges. These cartridges provide safe, reproducible and economical alternatives to in-lab packed glass columns and solve many practical problems associated with flash purification. However, care must be taken to choose the right cartridge to maximize your success.

Silica particles: The heart of flash chromatography

Even though it is a relatively “quick and dirty” technique, flash is still a form of liquid chromatography and all the rules regarding speed, capacity and resolution that apply to HPLC columns apply to it as well. The heart of flash chromatography is the cartridge which is typically packed with unmodified or C18-modied silica gel. The physical properties of the silica gel play a significant role in the quality of the flash separation. In this article we will discuss the effects of three physical aspects of the silica particle:

• Particle shape
• Particle size and size distribution
• Surface area

These properties affect the resulting chromatography in terms of:

• Backpressure, which affects speed of the separation and the types of pumps required
• Capacity and retention, which affect how much sample can be separated in one injection
• Efficiency and resolution, which effect final sample concentration and purity

Four different silicas were evaluated: two spherical and two irregular. Physical properties of the silicas are found in Table 1 while photomicrographs appear in Figure 1. Spherical and irregular silica were obtained from various flash chromatography suppliers. VersaFlash^™ cartridges packed with spherical silica.

The VersaFlashTM system

The Supelco VersaFlash^TM Station used in these experiments accepts cartridges of different sizes and lengths. Cartridge change-out is quick and easy and all materials that are in contact with the sample and eluants are inert and durable Teflon^®, PEEK or polypropylene.

Backpressure

Particle shape, size and size distribution affect backpressure (along with compressibility and porosity which are not considered here). To evaluate the effect of these parameters on backpressure, methanol was pumped through the cartridges at 100 mL/min. The pressure was measured with an in-line pressure gauge from Supelco. Results are presented in Figure 2. Two observations are noteworthy. First, Spherical 1 with twice the particle size of Spherical 2 gave roughly half the backpressure. Second, although the particle sizes of Spherical 1 and Irregular 1 are similar, the backpressure of Spherical 1 is 33% lower. Surprisingly, the backpressure of Spherical 2 is even lower than that of Irregular 2 although its particle size is 45% smaller, possibly due to the presence of fines in Irregular 2.

Capacity and retention

Preparative materials should have high capacity to maximize the yield and concentration of purified compounds. The breakthrough method was used to measure the capacity of each type of silica in this study. Silica was packed into a standard cartridge and a solution of benzyl alcohol in dichloromethane was pumped through. Once breakthrough of benzyl alcohol was detected, the flow was stopped and the amount of benzyl alcohol adsorbed in the cartridge was calculated. Results are shown in Figure 3.

Although the surface areas of the four silicas are similar, their capacity for benzyl alcohol is quite different. The two spherical silicas have more than 40% higher capacity than the two irregular silicas. Two factors likely contribute to this difference. First, because of the high packing density of the spherical particles, more material can be packed into each cartridge. Second, the silicas may differ in the degree of microporosity (<20Å). Micropores contribute to the total surface area, but surface inside the micropores is not actually accessible to analyte molecules.

Efficiency and resolution

Efficient preparative columns deliver high sample concentration (less peak dilution) and high sample purity (less overlap of peaks). The separation of toluene and benzyl alcohol shown in Figure 4 and toluene, 2,6-dinitrotoluene and benzanilide shown in Table 2 show that spherical silica particles gives higher efficiencies and better resolution than irregular silicas with similar pore and particle size. The highest efficiencies and best resolution were obtained on the smaller spherical silica, Spherical 2.

Benefits of spherical silica particles in VersaFlashTM cartridges

Compared to irregular particles, spherical silica particles generate lower backpressure and have greater mechanical stability, higher efficiency and better reproducibility. Surface areas and chemical properties are comparable. In spite of their benefits, Supelco is one of the very few suppliers of cartridges packed with spherical silica particles. Choose Supelco’s VersaFlashTM system of cartridges and equipment for fast and efficient flash separations.