Special Methods

Special Methods.—With some substances it is difficult to obtain good crystals by the methods already described. A method which frequently gives excellent results consists in dissolving the substance in some solvent, then adding a second solvent miscible with the first, but in which the substance is sparingly soluble. The first solvent is then gradually removed and the substance separates out—usually in the crystalline form. If the first solvent is the more volatile in air, spontaneous evaporation in air may diminish its concentration in the solution. The solution may be placed in a desiccator over some substance which absorbs the first solvent but not the second in this way water may be removed from a water-alcohol solution by solid caustic potash or quicklime. 

Another method—applicable when the substance is soluble in alcohol and in ether, but insoluble in water—consists in making a saturated solution in cold alcohol, adding water until considerable precipitation has taken place, then adding ether until the precipitate has redissolved, and finally allowing the ether to diminish by spontaneous evaporation. 

When a substance is soluble without change in concentrated sulphuric acid, but insoluble in water, a saturated solution in the former medium when left exposed to water-vapour—say, side by side with a vessel of water under a bell-jar—gradually absorbs water, and the substance frequently separates out in crystalline form. 

The purification of many products can be facilitated by distillation, prior to crystallisation, provided they distil without decomposition. Generally it is preferable to conduct the distillation under reduced pressure (p. 26). 

In addition to the ion sources described, there are other mass spectrometric methods for trace analysis of metals. Some of them are only used in exceptional cases and others are still under instrumental and methodological development. 

All elaborations made cannot and shall not claim to be exhaustive in any form. There are numerous other methods, such as the failure mode and effect analysis, which is preferably applied to the investigation of signal processing devices, or the human error analysis. 

Especially the last-mentioned is currently undergoing tremendous development. For certain other branches, for example the aviation and space industry, it is already well developed. But in respect to the chemical process industry its development is still in a very initial phase. 

Further semi-quantitative methods are the so-called index methods. Examples are the DOW-Fire and Explosion Index and the Mond-Hazard Index. They allow a relative scaling of different plants and process in quite a rigorous way concerning their hazard potential. 

In the examination of optically active compounds, optical rotational dispersion (ORD) and circular dichroism (CD) have been applied with success [111], Analysis took place in a conventional way extracting samples out of the reaction solution with off-line analysis in CD equipment. 

NMR equipment has also been used in kinetic examinations. The recent development of pulse Fourier spectroscopy allows the application of NMR even to solids and in flow systems. Thus, C-NMR spectroscopy can offer the advantage of monitoring chemical pathways. Even quantitative results can be achieved to determine rates of reaction [112]. 

The determination of trace elements such as Pb, Cd, Zn, Cu, As, Se, and Hg in environmental or clinical samples is often required at sub p.p.m. levels, the extreme limits of sensitivity for conventional AAS. At these low concentrations these elements can be readily determined by graphite furnace AAS. However, GF-AAS is relatively expensive, time-consuming, and in some cases too sensitive (for example, Zn in serum) a method. Typically, the measurement takes 2 to 3 minutes by GF—AAS, while by FAAS it takes 10 seconds or less. 

A number of methods have been described for improving the sensitivity of conventional FAAS in order to allow the analysis without resorting to more expensive techniques. Best known of these techniques are hydride generation, cold vapour, semi-flame (Delves cup, tantalum boat), and slotted tube atom trap (STAT) methods. 

Some elements cannot be determined by conventional AAS. The most suitable lines of non-metals (halogens, S, P, C, O, N) are located in the 

Electronic derivative obtained from the analog signal by differentiation and attenuation circuits direct on-line spectra higher derivatives possible derivative as a function of time and not of wavelength 

Computed the digitalized data are stored and the derivative is calculated direct deriv.itive as a function of wavelength original spectrum is not lost use of various algorithms optimization of the selected parameters necessity for an integrated computer or data station 

Each differentiation step leads in principle to an increase in noise, so that no additional information can be obtained by this mathematical procedure, although in some cases this form of spectral manipulation offers a possible way of revealing information hidden in raw data. However, as implied by the word manipulation, the final result is affected by the procedure used. 

The potential and limitations of derivative spectroscopy are described in many literature references. which also include several examples of its use [7], [186], [189], 

Derivative spectroscopy can be applied to fluorescence and fluorescence excitation spectra [188], It is also used in chromatography in the search for peak maxima, and in interferometric measurements for determining minima and maxima in interference spectra [124]. A typical application is the determination of phenol in water (Fig. 38) [190], 

Romijn (1897) first showed that aldoses are quantitatively oxidized by iodine in weakly alkaline solution under carefully controlled conditions. Ketoses and nonreducing sugars are only slightly attacked. Equations illustrating the reaction are given below (see also Chapter VI). 

Part of the hypoiodite is converted into iodate and iodide, the amount depending on the concentration, the time, and the temperature  

Since sodium iodate cannot oxidize the sugar in alkaline solution, some active iodine is lost as far as the sugar oxidation is concerned. If the entire quantities of alkali and iodine are admitted simultaneously, much iodine is transformed to iodate and a deficiency may result for the sugar oxidation. If iodine is present in too great an excess, over-oxidation can occur, and the alcoholic groups are slowly oxidized to carboxyl or carbonyl groups. 

Although some iodine may be lost by the side reaction, this iodine is measured along with the excess when the solution is acidified and titrated with thiosulfate  

Slater and Acree found that the iodine consumption can be confirmed by titrating with alkali the free acid left after the completion of the thiosulfate titration  

Several features of this type of reaction are notable. In the simple case shown, as in a classical resolution, the maximum yield of one product is 50% and the e.e. actually varies as the reaction progresses due to the kinetics of the system. If, however, the reaction is carried out under conditions in which the enantiomers of the substrate can interconvert (racemisation), the entire substrate can in principle be converted to the enantiomerically pure product and the e.e. of the product then remains constant throughout the course of the reaction. A good illustration of this point is provided in section 6.5.1. 

Many of the most useful applications of enzymes in asymmetric synthesis involve kinetic resolution and an example is the hydrolysis of ( )-A -acetylphenylalanine methyl ester (43) with a-chymotrypsin to give the (S)-acid (44) and the unchanged (/ )-ester (45). Very often, as in this case, we can make use of either of the two products once they have been resolved by a further simple non-asymmetric chemical step (here hydrolysis of (45) to give the (/ )-acid). 

The other important type of kinetic resolution is that in which the chiral reagent or catalyst discriminates between two enantiotopic groups in an achiral substrate. This may be thought of as a kinetic resolution within the same molecule and the substrate can be completely converted to a single enantiomeric product. Thus diester (46) is hydrolysed by pig liver esterase (PLE) to give exclusively the (5)-enantiomer of (47). A drawback of the internal kinetic resolution is that it may not be possible to find a catalyst to obtain the opposite 

An important development in recent years has been the introduction of more sophisticated methods which, on the face of it, combine elements of the first-, second-, third- and fourth-generation methods described in the last section. Thus we can, for example, react a chiral substrate with a chiral reagent. This approach, pioneered by Masamune,Pi is described as multiple asymmetric induction and is particularly valuable in reactions where two new stereogenic units are formed simultaneously. In the example which follows, the aldol reaction between chiral aldehyde (51) and a boron enolate to give (53) and (54) is considered. As it stands this is a first-generation method since the chiral substrate (51) reacts with the achiral enolate to give 

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The Debye treatment is not easily extended to higher concentrations and special methods are required to... 

MD, one needs to use multiple time step methods to ensure proper handling of the sprmg vibrations, and there is a possible physical bottleneck in the transfer of energy between the spring system and the other degrees of freedom which must be handled properly [199]. In MC, one needs to use special methods to sample configuration space efficiently [200, 201]. 

For complexes with high metal oxidation states, special methods are used, since these complexes can only exist with certain ligands (see above). 

Several empirical approaches for NMR spectra prediction are based on the availability of large NMR spectral databases. By using special methods for encoding substructures that correspond to particular parts of the NMR spectrum, the correlation of substructures and partial spectra can be modeled. Substructures can be encoded by using the additive model greatly developed by Pretsch [11] and Clerc [12]. The authors represented skeleton structures and substituents by individual codes and calculation rules. A more general additive model was introduced... 

Special methods are available for particular classes of compounds, Hinsberg s method of separating primary, secondary and tertiary amines (p. 249)-... 

The acid prepared as above is the Irans isomer isocrotonic acid is produced by special methods. 

There are many special methods to making heterocycles if you want to read about them, see Tedder, part 3, pp.115-131 and 205-220, or Norman, Chapter 18, p.5SS. We are more interested in applying these general methods to molecules in which a heterocyclic ring is only part of the problem. How would you make TM 263 from simple starting materials ... 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

Best Synthetic Methods is now 10 years old, is a family of 16 volumes and has been well received by the majority of chemists as a valuable aid in their synthetic endeavours, be they academic or commercial. The focus of the series so far has been on special methods, reagents or techniques. This volume is the first of a new sub-series with a focus on heterocycles and their synthesis. It is amazing the extent to which each heterocyclic type has its own specialized synthetic methodology. Whether the chemist is endeavouring to make a heterocycle by ring synthesis or wishes to introduce specific substituents, it is the intention that this new development will serve their needs in a practical, authoritative, fully illustrative and compact manner. Richard Sundberg is an authority on indole chemistry and it is a pleasure to have such a noted heterocyclist to initiate this venture. 

A-4-Thiazoline-2-ones and ring substituted derivatives are usually prepared by the general ring-closure methods described in Chapter II. Some special methods where the thiazole ring is already formed have been used, however. An original synthesis of 4- 2-carboxyphenyl)-A-4-thiazoline-2-one (18) starting from 2-thiocyanato-2-halophenyl-l-3-indandione (19) has been proposed (Scheme 8) (20, 21). Reaction of bicyclic quaternary salts (20) may provide 3-substituted A-4-thiazoline-2-one derivatives (21) (Scheme 9) (22). Sykes et al. (23) report the formation of A-4-thiazoline-2-ones (24) by treatment ef 2-bromo (22) or 2-dimethylaminothiazole (23) quaternary salts with base (Scheme 10). 

We will not discuss the preparation of cumulated dienes They are prepared less readily than isolated or conjugated dienes and require special methods... 

Lactones whose rings are three or four membered (a lactones and p lactones) are very reactive making their isolation difficult Special methods are normally required for the laboratory synthesis of small ring lactones as well as those that contain rings larger than SIX membered... 

Section 20 5 Acid anhydrides may be prepared from acyl chlorides m the laboratory but the most commonly encountered ones (acetic anhydride phthahc anhydride and maleic anhydride) are industrial chemicals prepared by specialized methods... 

A new field of transfusion medicine, cell therapy, has developed with the better understanding of the function of different cell types ia the body. In cell therapy, various malignancies are treated by transfusion of specific cell types from blood. Therefore, more and more specialized methods for separating blood iato the various components are required. 

Ionomer resins are produced in multiple grades to meet market needs, and prospective customers are provided with information on key processing parameters such as melt-flow index. Nominal values for many other properties are Hsted in product brochures. The ASTM test methods developed for general-purpose thermoplastic resins are appHcable to ionomers. No special methods have been introduced specifically for the ionomers. 

R. B. McLaughlin, Special Methods in Tight Microscopy, McCrone Research Institute, Chicago, HI., 1977. 

Tables 4—6 Ust ASTM methods used for the characterization of PB and PMP. A number of specialized methods were developed for testing particular articles manufactured from polyolefins several of these determine the performance of PB and PMP film, including the measurement of the film s dart impact strength and tear strength. Dart impact strength is measured by dropping a heavy dart with a round tip on a stretched film. Tear resistance, which reflects the film s resistance to tear propagation, is measured with the Ehnendorf tear tester. Two values for the tear strength are usually reported, one in the machine dkection of the film and the other in the transverse dkection. Pipes manufactured from PB are tested by pressurizing them internally with water the time-to-burst failure is determined at various temperatures (46). The standard test method for haze and luminous transmittance (ASTM D1003) is used for the measurement of PMP optical characteristics.

Owiag to incomplete halogea absorption, iodiae values for conjugated acid oils by the usual methods (Wijs, Hanus, etc) are both low and variable. The tme value of fresh tung oil, as determined by a special method (13), is 248—252 that of oiticica oil is 205—220. 

Although the most sensitive line for cadmium in the arc or spark spectmm is at 228.8 nm, the line at 326.1 nm is more convenient to use for spectroscopic detection. The limit of detection at this wavelength amounts to 0.001% cadmium with ordinary techniques and 0.00001% using specialized methods. Determination in concentrations up to 10% is accompHshed by solubilization of the sample followed by atomic absorption measurement. The range can be extended to still higher cadmium levels provided that a relative error of 0.5% is acceptable. Another quantitative analysis method is by titration at pH 10 with a standard solution of ethylenediarninetetraacetic acid (EDTA) and Eriochrome Black T indicator. Zinc interferes and therefore must first be removed. 

Other mixed esters, eg, cellulose acetate valerate [55962-79-3] cellulose propionate valerate [67351-41-17, and cellulose butyrate valerate [53568-56-2] have been prepared by the conventional anhydride sulfuric acid methods (25). Cellulose acetate isobutyrate [67351-38-6] (44) and cellulose propionate isobutyrate [67351-40-0] (45) have been prepared with a 2inc chloride catalyst. Large amounts of catalyst and anhydride are required to provide a soluble product, and special methods of delayed anhydride addition are necessary to produce mixed esters containing the acetate moiety. Mixtures of sulfuric acid and perchloric acid are claimed to be effective catalysts for the preparation of cellulose acetate propionate in dichi oromethane solution at relatively low temperatures (46) however, such acid mixtures are considered too corrosive for large-scale productions. 

Liquid Diffusivity Liquid diffiisivities are in general not as accurately predicted as vapor diffiisivities, and specialized methods have been developed. References to each method determined to be accurate are given, but only the most common methods will be presented. 

And we are still learning how best to fabricate and use them. As emphasised in the last chapter, the mechanical properties of polymers differ in certain fundamental ways from those of metals and ceramics, and the methods used to design with them (Chapter 27) differ accordingly. Their special properties also need special methods of fabrication. This chapter outlines how polymers are fabricated and joined. To understand this, we must first look, in slightly more detail, at their synthesis. 

Liquids, directly solids, following dissolution solids, surfaces, and thin films with special methods (e.g., laser ablation)... 

The solubility parameter is thus an experimentally determinable property although special methods are necessary with polymers, which cannot normally be vaporised without decomposition. Such methods are discussed in Section 5.3.3. 

Vacancy chromatography is a special method of development that can provide both negative and positive peaks in the chromatogram. It is not commonly used, although... 

C-Toxiferine II. This base was obtained from curares from Urbana and Caracas, sometimes accompanied by toxiferine II (see below), and was isolated by a special method as the chloride, C20H25ON2CI, [a] -f- 72-1° (H2O). The picrate forms hexagonal prisms, m.p. 215° (dec.). 

A phytochemical investigation of taxine in the yew has been conducted by Kuhn and Schafer, who have devised special methods for the detection, estimation and purification of the alkaloid. Masson states that Taxus canadensis contains an alkaloid giving the colour reactions of taxine but different from it in being crystalline and having m.p. 238-9° no ephedrine was present. 

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