Laboratory Preparation and Manufacture

In Chapters 13 and 14 of this book the applications of conventional chemical catalysts were described. The use of enzymes or whole cells as catalysts for chemical transformations is well known. They can bring about various reactions at ambient temperature and pressure and afford high reaction velocities. In fact, enzymatic reaction sequences may be designed to give the ideal efficiency embodied in the second law of thermodynamics. Thus, hundreds of compounds that are very difficult to prepare by purely chemical methods may be obtained quite readily and economically with the help of enzymes. Until recently, most laboratory investigations and manufacturing processes employed soluble enzymes in dilute aqueous solutions. Before use, the required enzyme must be obtained from biological sources as a concentrated extract. It is not uncommon for a particular type of cell to contain many proteins in addition to the one desired. Therefore, the purification and concentration of enzymes in preparation for use is a very cumbersome process. When used in solution, enzyme catalysts are invariably lost after each batch operation. The use of immobilized enzymes and whole cells has been proposed as a means that could eliminate such losses and preserve hard won stocks of specialized enzymes. 

This research was prepared as an account of work sponsored by the United States Air Force Research Laboratory, Materials and Manufacturing Directorate, Airbase Technologies Division (AFRL/RXQ), but the views of authors expressed herein do not necessarily reflect those of the United States Air Force. 

Optical Techniques. The most important tool in a museum laboratory is the low power stereomicroscope. This instmment, usually used at magnifications of 3—50 x, has enough depth of field to be useful for the study of surface phenomena on many types of objects without the need for removal and preparation of a sample. The information thus obtained can relate to toohnarks and manufacturing techniques, wear patterns, the stmcture of corrosion, artificial patination techniques, the stmcture of paint layers, or previous restorations. Any art object coming into a museum laboratory is examined by this microscope (see Microscopy Surface and interface analysis). 

Ketones are an important class of industrial chemicals that have found widespread use as solvents and chemical intermediates. Acetone (qv) is the simplest and most important ketone and finds ubiquitous use as a solvent. Higher members of the aUphatic methyl ketone series (eg, methyl ethyl ketone, methyl isobutyl ketone, and methyl amyl ketone) are also industrially significant solvents. Cyclohexanone is the most important cycHc ketone and is primarily used in the manufacture of y-caprolactam for nylon-6 (see Cyclohexanoland cyclohexanone). Other ketones find appHcation in fields as diverse as fragrance formulation and metals extraction. Although the industrially important ketones are reviewed herein, the laboratory preparation of ketones is covered elsewhere (1). 

Processes that are essentially modifications of laboratory methods and that allow operation on a larger scale are used for commercial preparation of vinyhdene chloride polymers. The intended use dictates the polymer characteristics and, to some extent, the method of manufacture. Emulsion polymerization and suspension polymerization are the preferred industrial processes. Either process is carried out in a closed, stirred reactor, which should be glass-lined and jacketed for heating and cooling. The reactor must be purged of oxygen, and the water and monomer must be free of metallic impurities to prevent an adverse effect on the thermal stabiUty of the polymer. 

Boron Triiodide. Boron ttiiodide is not manufactured on a large scale. Small-scale production of BI from boron and iodine is possible in the temperature range 700—900°C (70—72). Excess I2 can be removed as Snl by reaction with Sn, followed by distillation (71). The reaction of metal tetrahydroborates and I2 is convenient for laboratory preparation of BI (73,74). BI can also by synthesized from B2H and HI in a furnace at 250°C (75), or by the reaction of B with excess Agl or Cul between 450—700°C, under vacuum (76). High purity BI has been prepared by the reaction of I2 with mixtures of boron carbide and calcium carbide at elevated temperatures. 

Commercial manufacture of methyl bromide is generally based on the reaction of hydrogen bromide with methanol. For laboratory preparation, the addition of sulfuric acid to sodium bromide and methanol has been used (80). Another method involves the treatment of bromine with a reducing agent, such as phosphoms or sulfur dioxide, to generate hydrogen bromide (81). 

There are three general methods of interest for the preparation of vinyl chloride, one for laboratory synthesis and the other two for commercial production. Vinyl chloride (a gas boiling at -14°C) is most conveniently prepared in the laboratory by the addition of ethylene dichloride (1,2-dichloroethane) in drops on to a warm 10% solution of sodium hydroxide or potassium hydroxide in a 1 1 ethyl alcohol-water mixture Figure 12.1). At one time this method was of commercial interest. It does, however, suffer from the disadvantage that half the chlorine of the ethylene dichloride is consumed in the manufacture of common salt. 

Although the asymmetric hydrogenation route to 3,3-diphenylalanine via this modified substrate preparation was not developed further, Dowpharma had a requirement to rapidly develop and scale up the manufacture of a related 3,3-diarylalanine product. The work to 3,3-diphenylalanine centred around substrate preparation and removal of impurities leading to high activity associated with the PhanePhos catalyst system allowed for a facile transfer from laboratory scale experiments to the commercial manufacture of the related diphenylalanine derivative by a robust, reproducible and scaleable procedure. 

The business of BioZone Laboratories concerns development, manufacturing, and marketing of products and technologies, such as drugs and preparations, cosmetics, and nutritional supplements. All product lines are supported by proprietary technologies, and research and development activities are considered to be of a core importance for the business. The IP estate is also available for commercialization, particularly in the prescription area, for which several drug delivery systems and a prescription version of Inflacin were developed. 

In the first phase of their research, Squibb tested a short-chain peptide isolated from the venom of the viper Bothrops jararaca, with which Vane was working in the laboratory, in human volunteers and showed that it did, indeed, inhibit the conversion of angiotensin I to angiotensin II after intravenous injection. The peptide was also shown to reduce blood pressure in patients when injected. Since the vast majority of peptides cannot be absorbed from the GI tract, Squibb scientists set out to prepare a nonpeptide compound that could be used orally and manufactured at acceptable cost. The design of a true peptidomimetic that became orally active had not been accomplished at that time. Squibb then carried out... 

Whereas commercially manufactured products are required to possess an expiration date, compounded products are assigned a beyond-use date. There are numerous sources of information that can be utilized for determining an appropriate beyond-use date, such as chemical companies, manufacturers literature, laboratory data, journals, and published texts on the subject. Generally, most pharmacists prepare and dispense small quantities of compoimded products, recommend storage at room, cool, or cold temperatures, and use a conservative beyond-use date. 

SOPs can be both general and specific. Examples of general laboratory operations include how to characterize an analytical standard, how to record observations and data, and how to label reagents and solutions. Most laboratory operations even have an SOP for writing and updating SOPs. Examples of specific laboratory operations include the preparation and analysis of a specific company s product or raw material, the operation and calibration of specific instruments, and the preparation of specific samples for analysis. Often, SOPs are based on published methods, such as those found in scientific journals, in application notes, and procedures published by instrument manufacturers, or in books of standard methods, such as those published by the American Society for Testing and Materials (ASTM) and the Association of Official Analytical Chemists (AOAC). The published... 

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