Automated preparative chromatography

The instrument needed to perform automated preparative chromatography (which will hereafter be referred to as autoprep) in the desired format is based upon a standard high-pressure binary gradient instrument. The most important feature of the instrument for our particular requirements was the ability to operate from the microtitre plate sample format. This is important for combinatorially derived samples as it appears to be the standard format. It also becomes the most sensible arrangement for collecting large numbers of fractions within a reasonable size collection tray footprint . 

Eglinton et al. [688] described a practical approach for isolation of individual compounds from complex organic matrices for natural abundance radiocarbon measurement. This approach uses an automated preparative capillary gas chromatography (PCGC) to separate and recover sufficient quantities of... 

The development of this technique has proceeded along several independent paths with two principal lines being elemental analyzer-IRMS and capillary gas chromatography-IRMS. In elemental analyzers, samples are combusted to CO2, N2, SO2, and H2O, which are either chemically trapped or separated on GC columns. The advantages of these techniques are an automated preparation with low costs per sample and a large sample through-put. 

This robotic sample preparation and counting technology, together with mechanical improvements in the chemical separation system, has resulted in an automated column chromatography system that can run almost autonomously, whereas several people were required to operate the ARCA II system for a transactinide chemistry experiment. 

The application of preparative and scale up chromatography and the strategies for the development of process chromatography as a unit operation will be discussed in detail. The development and application of an automated preparative HPLC system for purification of small amounts of research compounds by the chemists themselves will be also described. 

The development and industrial application of automated preparative HPLC 8.43 Validation of the preparative chromatography... 

Automation allows batch chromatography to be run as a continuous process. Multiple injections using a separate pump and fraction collection provide an opportunity for continuous unattended operation. In iso-cratic separations, sample injection is often made before previously injected product elutes from the column, thus reducing cycle time and solvent consumption. Continuous and automated processes are always used with smaller columns and lower amounts of expensive enantioselective stationary phases. One of the future goals for modern PHPLC optimization would be the creation of software that would allow computer simulation modeling of nonlinear effects in preparative chromatography. 

To improve the throughput for characterizing combinatorial libraries, automated approaches are being developed [29]. Some automated approaches include the combination of peak detection with preparative chromatography and fractionation... 

Purification by automated flash chromatography, preparative HPLC... 

Typical procedure. l-Methyl-d-cyanobutyl N-[l-(l-naphthyl)ethyl]carbamates 614 (R = Me, n = 4) [439]. Procedure A A stirred solution of 5-cyanopentan-2-ol (8.0 g, 70.8 mmol), (R)-( —)-l-(l-naphthyl)ethyl isocyanate (13.9 g, 70.8 mmol), dry benzene (150 mL), and two drops of dimethylethanolamine catalyst was heated at reflux under N2 for 24 h. The solvent was then removed in vacuo, and the crude diastereomeric carbamates were completely separated by chromatography (on acidic alumina, eluting with CHCla/hexane, 2 1) using an automated preparative LC system. A total of 8.9 g (81%) of the high R( (R,R) diastereomer was collected as a yellow viscous oil. 

Verette, E., F. Qian, and F. Mangani. 1995. On-line dialysis with high-performance liquid chromatography for the automated preparation and analysis of sugars and organic acid in foods and beverages. J. Chromatogr. A 705 195-203. 

Preparation of the monobrominated bisquinolone. A mixture of 109 mg (0.25mmol) of 4,4 -bis(6,7-dimethoxy-l-methylquinolin-2(l/7)-one), 111.2mg (0.625mmol, 2.5 equiv) of A-bromosuccinimide (NBS), and 0.6 mL of DMF in a vial equipped with a magnetic stir bar was stirred for 35 min at room temperature. The reaction was quenched by addition of ice water and was filtered. The resulting crude product mixture was purified by automated flash chromatography using EtOAc/CHjCN as eluent to give 80 mg (62%) of the monobrominated material as a yellow solid. 

Section I of this book includes chapters on the principles and practice of PLC. After this introductory Chapter 1, Chapter 2 provides information on efforts undertaken to date in order to establish the theoretical foundations of PLC. With growing availability and popularity of modem computer-aided densitometers, separation results can be obtained in digital form as a series of concentration profiles that can be relatively easily assessed and processed. From these, relevant conclusions can be drawn in exactly the same manner as in automated column chromatographic techniques. Efforts undertaken to build a theoretical foundation of PLC largely consist of adaptation of known strategies (with their validity confirmed in preparative column liquid chromatography) to the working conditions of PLC systems. 

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