Trouble shooting

In Section 2.2.11, possible failures during the freeze-drying process are classified in four categories and the preventions and necessary actions briefly discussed. In this chapter, some unexpected or undesirable events are studied which, by experience, may happen. The problems listed here are selected from the course of the freeze-drying process. A breakdown of single components, e.g. pumps, compressors or valves is not included. The list will be incomplete, but an attempt has been made to mention some of the more frequent events. The problems with leaks and their hunting is discussed in Sections 2.2.9 and 2.2.11. 

Some reactions will not work, for proper chemical reasons associated with the substrate. These may or may not be obvious (many things become obvious with hindsight). Do not jump to the conclusion that you have encountered such a reaction. Before you can conclude that this is the case a number of possibilities must be explored. 

The first and most obvious is to make sure that the starting material is pure, dry, and free from solvents, and that it is indeed what you think it is. A critical perusal of all the analytical and spectroscopic data will usually be sufficient. If you have used several batches of starting material then do make certain that the spectra which you check are from the batch which you used in the failed reaction. If necessary, re-run the spectrum to ensure that the starting material has not partially decomposed, or picked up moisture. 

If the starting material is decomposed under the reaction conditions, then consider carefully any possible chemical reasons which might be responsible. For example, basic conditions might be causing deprotonation and/or elimination at an undesired site or sites in the molecule, and acidic conditions might be responsible for unexpected cyclisation or protecting group loss. There are often several possible sources of instability towards a particular set of reaction conditions, and it will be necessary to examine all possibilities. 

It is likely that the reaction will be closely related to a known process, and if this is so then be critical in your comparison of reaction conditions and reactants. For example if an enolate alkylation is being attempted, but appears not to work at a temperature below which the enolate decomposes, then consider the reactivity of the alkylating reagent Is it really as reactive as in the example which you are following If not, then the appropriate change wiU need to be made. 

The single most important piece of advice in trouble-shooting a reaction is to be certain that you identify the problem, before you try to remedy it. This might seem to be obvious, but it is surprising how often this advice is not followed. Try hard to keep an open mind, to analyse the problem critically and logically, and to gather evidence to support your identification of the problem. When you have a clear idea what the problem actually is, you can begin to think of potential solutions which are likely to have the desired effect 

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Microscopists in every technical field use the microscope to characterize, compare, and identify a wide variety of substances, eg, protozoa, bacteria, vimses, and plant and animal tissue, as well as minerals, building materials, ceramics, metals, abrasives, pigments, foods, dmgs, explosives, fibers, hairs, and even single atoms. In addition, microscopists help to solve production and process problems, control quaUty, and handle trouble-shooting problems and customer complaints. Microscopists also do basic research in instmmentation, new techniques, specimen preparation, and appHcations of microscopy. The areas of appHcation include forensic trace evidence, contamination analysis, art conservation and authentication, and asbestos control, among others. 

Process trouble shooting. Analysis or separation system operation and malfunc tion, examination of composition profiles, and tracking of trace impurities with implications for corrosion and process specifications. 

Sohre, J., Reliability Evaluation for Trouble-Shooting of High-Speed Turbomachinery, ASME Petroleum Mechanical Engineering Conference, Denver, Colorado. 

Harrison, M. E. and France. J. J., Trouble-Shooting Distillation Columns," parts 1—4, Chemical Engineering, March-June, 1989. 

Pressure drop on the low side, but adequate Harrison, M. E. and J. J. France, Trouble-Shooting ... 

Design or trouble shooting During the design stage an on-site experiment with the actual equipment is not usually possible. Numerical prediction may then be simpler. However, for trouble shooting, field measurements are strongly recommended, ideally complemented by simulations techniques. 

Very often, voluminous procedures gather dust in cabinets where they have lain since the system was commissioned. For simple skiU-based tasks carried out by experienced workers, no procedural support will be necessary. Other activities such as trouble shooting or diagnosis may, as discussed in Chapter 2, involve the use of formal or mformal rules which are used infrequently. In these cases some form of job aid or checklist is the most effective type of procedure. 

Vargas, K J., Trouble-Shooting Compression Refrigeration Systems, Chem. Eng., McGraw-Hill, Inc., p. 137, March 22, (1982). All rights reserved. 

Failure analysis statistics have consistently shown that many machinery components failures can be directly attributed the equipment being operated outside of design parameters or unintended conditions. Most failure analysis and trouble-shooting activities are usually post-mortem and commence after installation and start-up of the equipment. The maintenance phase is now in motion, and failure analysis and trouble-shooting is now an integral part of that phase. 

Supelco Trouble Shooting Guide 792. Supelco, Inc., Supelco Park, Bellefonte, PA 16823-0048... 

Even without the current outsourcing trends, it has always been difficult for service companies to find sufficient numbers of well-trained, experienced, and motivated field representatives. This is because the range of water treatment problems and potential solutions are very wide and the business involves the marketing of many different types of chemicals and equipment, coupled with consulting work and innovative trouble shooting. 

The telephone is still one of the primary means of communication for clinical trial personnel. The telephone is used for both voice and digital communications. Voice communication is the normal person-to-person telephone call. Data communication with the telephone is the transmission of digital data from one location to another. Various software packages have been developed for this purpose. Using a voice modem connected to a telephone, a user on a local computer can connect to another remote computer that has a modem connected to a telephone and download or upload data files. Local and remote users can also communicate with text messages. The local computer operator can even control the remote computer for trouble-shooting or system update. 

SRM 2390 can be used in several different ways depending on quality assurance requirements. Components of the SRM are designed to provide assurance that each step of the RFLP protocol is functioning properly, but they can also be used for trouble shooting, for calibrating equipment, and for testing the efficacy of new lots of reagents. 

Material balances are also useful tools for the study of plant operation and trouble shooting. They can be used to check performance against design to extend the often limited data available from the plant instrumentation to check instrument calibrations and to locate sources of material loss. 

Decide and show those ancillary instruments needed for the monitoring of the plant operation by the operators and for trouble-shooting and plant development. It is well worthwhile including additional connections for instruments which may be needed for future trouble-shooting and development, even if the instruments are not installed permanently. This would include extra thermowells, pressure tappings, orifice flanges, and extra sample points. 

Additional temperature indicating or recording points should be included up the column for monitoring column performance and for trouble shooting. 

Historical operating data is retained in the computer memory. Averages and trends can be displayed, for plant investigation and trouble shooting. 

Motors support for a long-range scientific study of the poisonous gasoline additive, tetraethyl lead. Besides trouble-shooting for various Du Pont departments, Carothers published 60 papers and was listed as the inventor or coinventor of 69 U.S. patent applications during his nine years at Du Pont. Research and development were so new to American corporations that Carothers assistants drafted and he edited patent applications for Du Pont lawyers. You were supposed to be so on top of the literature that you knew whether this was something new or not.. . . Those patents are really classical scientific papers, Hill explained. Carothers considered himself unfit to be a clerk or inventor, but he dominated Du Pont s patent application process for almost a decade. 

The analysis of each EO distribution of a multiple alkyl AE should facilitate better characterization protocols. One-dimensional NPLC may provide sufficient resolution for less complicated AE (i.e., Novel II 1412-70 and Brij 35), but 2DLC offers the selectivity to display the EO distribution of each end group independently, which is neither easy nor unambiguous to extract from one-dimensional data. 2DLC is a powerful technique not only to separate materials, but also to aid in identification, characterization, analytical trouble shooting, synthesis optimization, and quality control. 

NMR is predictive of reactivity within a series Within a set of common donors (i.e., galactose) in which the C2 position is constant, the H chemical shift of the anomeric carbon appears to be a good predictor of relative reactivity. Little correlation is found when the C2 position is varied, or between different donor pyranoses. The extent to which this correlation will prove useful remains in question. We envision that its primary applicability may be in trouble shooting a failed synthesis when a complex donor does not behave as predicted. Checking the H NMR of the advanced intermediate may quickly reveal that the RRV value for the pyranose of interest is not as expected, and hence the reactivity is not as expected. 

Lastly, the need for potential trouble shooting bulk samples should be agreed to facilitate any out-of-specification (OOS) investigations (Worsham, 2010). 

Ion-pair liquid chromatography can be applied to the separation of a wide variety of compounds. However, the flexibility of the selection of eluent components can confuse the operation. Trouble-shooting solutions are summarized in Table 4.6. 

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