Semimicro preparations

The most difficult part of a semimicro preparation is the purification of the product. If the product is a solid, it may usually be purified by recrystallization or chromatography as described previously (pages 99 and 156). The amount of solvent should be kept to a minimum in recrystallization, so that a large portion of the material will not be lost in the mother liquors. If the product is a liquid, it is rarely possible to effect a good purification by distillation, and with quantities less than 500 mg, the holdup of most distillation apparatus becomes prohibitive. The most satisfactory method for the purification of small quantities of liquids is vapor-phase chromatography (page 165). This method is ideally suited for handling 10 to 500 mg of material and will provide a separation which can be matched by few other methods, with essentially no loss due to holdup. 

D) Preparation of Butanone (M.). The same procedure is used as in the semimicro preparation of butanone section (B). Arrange a 500 ml round-bottom or Florence flask for fractional distillation as shown in Figure 27. The stopper which connects the fractionating column to the flask has an opening for a separatory funnel. The condenser fits through an adapter to a receiving flask immersed in cold water or ice-salt mixture. 

B) Preparation of Glycine (M.). Use the same method as in section (A). Use a 500-ml Erlenmeyer flask and 10 times the quantities given for the semimicro preparation. After distillation of ammonia and further evaporation, the solution is treated with 0.5 g of charcoal and filtered. The residue is washed with 5 ml of hot water. The filtrate (about 100 ml) is placed in a beaker and 300 ml of methanol are added. After 24 hours the crude glycine is filtered, dried by suction, then pulverized while wet, suspended in 100 ml of methanol, and allowed to stand for an hour, with occasional stirring. The crystals are filtered, washed twice with 10 ml portions of methanol, and dried. The yield is about 25 g. The product prepared in this manner contains traces of ammonium chloride as impurities. If a very pure product is desired, the crystals are dissolved in 50 ml of boiling hot water, and the solution is treated with 1 g of charcoal and 0.5 g of Super-cel. It is then filtered with suction while hot and the solution diluted with 150 ml of methanol. The precipitated glycine is allowed to cool for an hour, filtered with suction, washed with 10 ml of methanol, and dried. The loss on recrystallization is 10-12 per cent. 

Under more vigorous reaction conditions, dinitration takes place with mixed acids. The semimicro preparation of 2,4-dinitrobromo-benzene illustrates this procedure. 

Standard Semi-micro Equipment. The authors have found, during many years, that a student provided with the following basic semimicro equipment will be enabled to carry out the majority of the small preparations described in this book. 

First, considerably greater emphasis has been placed on semimicro techniques and their application to preparations, separations, analysis and physical determinations such as those of molecular weight. We have therefore greatly expanded the section on Manipulation on a semi-micro scale which was in the Third Edition, and we have described many more preparations on this scale, some independent and others as alternatives to the larger-scale preparations which immediately precede them. Some 40 separate preparations on the semi-micro scale are described in detail, in addition to specific directions for the preparation of many classes of crystalline derivatives required for identification purposes. The equipment required for these small-scale reactions has been selected on a realistic basis, and care has been taken not to include the very curious pieces of apparatus sometimes suggested as necessary for working on the semi-micro scale. 

Chapter XII is concerned with Semimicro Technique. There can be little doubt that preparations on a smaller scale than has hitherto been customary have many advantages particular reference may be made to cost, time and bench space, all of which are important factors in teaching laboratories and also in training for research. Once the student has mastered the special technique, no difficulty should be experienced in adapting most of the preparations described in the book to the semimicro scale. A few examples of small-scale preparations are included together with a suggested list of experiments for an elementary course. 

In a semimicro synthesis selenophene is prepared from bis(trimethylsilyl)-1,3-butadiyn and NaHSe generated in situ from Se and NaBH4 in aqueous dimethylformamide.52 Other ring cyclization reactions have been performed... 

The application of periodate oxidation to a problem can best be considered in terms of an approach from two separate standpoints. The first generally involves the application of analytical techniques to semimicro quantities of material, and sometimes suffices to yield the desired information. After performing this preliminary, analytical investigation, the second or preparative phase may be undertaken. This entails use of much larger amounts of material, with the intention of isolating the end products of oxidation. If these are obtained, their properties should serve to confirm the results of the preliminary, analytical work and, if this is proved correct, the method is then available as a route to the desired synthetic compound. 

VI.5 TESTING FOR ANIONS IN SOLUTION ON THE SEMIMICRO SCALE The preliminary tests 7 and 8 with dilute sulphuric acid and with concentrated sulphuric acid will have provided useful information as to many anions present. For more detailed information, it is necessary to have a solution containing all (or most) anions free from heavy metal ions. This is best prepared by boiling the substance with concentrated sodium carbonate solution double decomposition occurs (either partially or completely) with the production of the insoluble carbonates of the metals (other than alkali metals) and the soluble sodium salts of the anions, which pass into solution. Thus, if the unknown substance is the salt of a bivalent metal M and an acid HA, the following reaction will occur ... 

VI.8 PREPARATION OF SOLUTION FOR CATION TESTING ON THE SEMIMICRO SCALE... 

Table VI.13 Separation of Groups IIA and IIB as well as separation of Group IIA cations on the semimicro scale The ppt. obtained with H2S in the presence of dilute HC1 ( 0-3m) may contain the sulphides HgS, PbS, Bi2S3, CuS, and CdS, and also As2S3, Sb2S3, and SnS2(l). Treat the ppt. with 1-5 ml of 2m KOH solution, and heat in a boiling water bath for 3 minutes with occasional stirring (CAUTION see Note 2). Add 4 drops freshly prepared saturated H2S water stir and centrifuge.

The book begins with a discussion of the basic physico-chemical aspects of reactions utilised in qualitative inorganic analysis. A description of laboratory equipment follows, and operations which include semimicro and micro techniques, and simple electrochemical, spectroscopic and chromatographic methods. The reactions of the most important cations and anions are described, followed by a treatment of systematic qualitative analysis. Sample preparation, dissolution and fusion of insoluble materials are treated in detail. A separate chapter deals with the reactions of less common ions, with guidelines to their separation and identification in the course of systematic analysis. Finally, a simplified course of qualitative analysis is given this chapter will be particularly useful where the time allocated to qualitative analysis is limited. 

Note The preparation of n-octane or n-decane by the action of sodium on alkyl halides is recommended only on a semimicro scale for beginners. The macro method involves the use of 10-15 g of sodium and therefore it is not recommended. Even the semimicro technic requires the use of 2-2.5 g of sodirnn, an amount which it is dangerous to use unless the student is very careful and follows directions. The preparation of n-decane is preferred for beginners. 

Note This experiment is better adapted to semimicro technic. The macro method may be used but difficulties are encountered by beginners. The use of Grignard reagent by the macro method is described in Experiment 36. The semimicro technic permits the introduction of the Grignard reagent early. Besides its use for the preparation of a hydrocarbon in the present experiment, it is used in Experiment 23 for the preparation of carbinols and Experiment 36 for the preparation of carboxylic acids. 

Note For semimicro work the student may choose between the preparation of ethyl and n-butyl ethers. The macro preparation of ethyl ether is not recommended for beginners, particularly vdien the group of students is large. 

B) Preparation of Ethyl Ether (M.). The method is the same as described in section (A). The quantities used are five times those given in the semimicro procedure. The apparatus shown in Figure 47 consists of a 500 ml distilhng flask heated on an asbestos-... 

Note If the semimicro method is used, sections (A) and (B) may be run simultaneously. The macro method is given only for nitrobenzene if that method is used for the other preparations the quantities given for the semimicro methods should be increased proportionately. 

The Grignard reagent is usually carbonated by passing dry carbon dioxide gas into the ethereal solution. In the present experiment solid carbon dioxide is used to avoid the rather long time required for carbonation with the gas. Although the yield is lowered, the carbonation is completed within five minutes. For semimicro work the preparation of benzoic acid is recommended for beginners. 

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