Fractional distillation, optical

Garene Manufacture. 3-Carene is obtained by fractional distillation of turpentine. Turpentine from the western United States and Canada averages about 25% 3-carene much of it is unutilised although it is obtained in high optical purity. Turpentines from the Scandinavian countries, the CIS, Pakistan, and India all contain significant quantities of 3-carene. 

Camphor was originally obtained from the camphor tree Lauras eamphora in which it appeared in the optically active dextro-rotary form. Since about 1920 the racemic ( ) mixture derived from oil of turpentine has been more generally used. By fractional distillation of oil of turpentine the product pinene is obtained. By treating this with hydrochloric acid, pinene hydrochloride (also known as bomyl chloride) may be produced. This is then boiled with acetic acid to hydrolyse the material to the racemic bomeol, which on oxidation yields camphor. Camphor is a white crystalline solid (m.p. 175°C) with the structure shown in Figure 22.3. 

Up to this point no evidence was forthcoming that any oneoffthe fenchenes prepared was pure, as the optical rotation of nearly every specimen was different. Wallach i has, however, more recently prepared fenchene by treating fenchyl-amine with nitrous acid. The resulting terpenes were separated by fractional distillation into two main portions, one of which had the following characters —... 

Deussen and Lewinsohn were the first chemists to show conclusively that at least two sesquiterpenes are present in this body. By repeated fractional distillation they separated it into two bodies having the following characters, suggesting that the former might be an optically inactive sesquiterpene, slightly contaminated with the optically active variety —... 

According to Read and Smith i piperitone is, under natural conditions, optically inactive. By fractional distillation under reduced pressure, it is prepared, by means of its sodium bisulphite compound, in a laavo-rotatory form. The slight laevo-rotation is probably due to the presence of traces of cryptal. By fractional distillation alone, it is usually obtained in a laevo-rotatory form whether this is due to decomposition products or not is unknown. Piperitone has a considerable prospective economic value, as it forms thymol by treatment with formic chloride, inactive menthone by reduction when a nickel catalyst is employed, and inactive menthol by further reduction. Its char-Mters are as follows —... 

The value of fractional distillation in the examination of essential oils cannot be overestimated. The various fractions may be examined and their specific gravities, optical rotations, and refractive indices determined. The combination of these figures will often give the experienced analyst the most useful information and save him many hours needless work. Experience alone, however, will teach the chemist to make the fullest use of the results so obtained. In most cases distillation under reduced pressure is necessary on account of the risk of decomposing the various constituents of the oil. The use of a Briihl receiver (or any similar contrivance), which is easily obtained from any apparatus maker. 

Although fractional crystallization has always been the most common method for the separation of diastereomers. When it can be used, binary-phase diagrams for the diastereomeric salts have been used to calculate the efficiency of optical resolution. However, its tediousness and the fact that it is limited to solids prompted a search for other methods. Fractional distillation has given only limited separation, but gas chromatography and preparative liquid chromatography have proved more useful and, in many cases, have supplanted fraetional crystallization, especially where the quantities to be resolved are small. 

If desired, the course of the reaction may be followed by means of the optical density of the reaction mixture at 235 m/. The ultraviolet spectrum of isophorone has a maximum at 235 mp (e 13,300) the ultraviolet spectrum of isophorone oxide has a maximum at 292 mju (e 43). A total reaction time of 4 hours under the conditions specified was found to be ample for the complete conversion of isophorone to its oxide. If the conversion is not complete, the product cannot be separated from the unchanged isophorone without recourse to precise fractional distillation. The absence of isophorone from the final product may be verified by examination of the spectrum at 235 mp. 

Optical fibres need to be free of impurities such as transition metal ions (see Chapter 8) and conventional methods of preparing silica glasses are inadequate. The sol-gel process is one way of forming fibres of sufficient purity (chemical vapour deposition. Section 3.7, is another). These processes use volatile compounds of silicon which are more easily purified, for example by fractional distillation, than silica. It is possible to produce silica fibres using a method similar to that studied in the nineteenth century, but with the geldrying time reduced from a year to a few days. Liquid silicon alkoxide (Si(OR)4), where R is methyl, ethyl, or propyl, is hydrolysed by mixing with water. 

The enantiomeric menthols have identical physical properties (apart from their specific rotation), but the racemates differ from the optically active forms in, for example, their melting points. Although the differences between the boiling points of the stereoisomers are small, the racemates can be separated by fractional distillation. Boiling points (in °C at 101.3 kPa) are as follows ... 

Production. In the past, (+)- and (-)-carvones were isolated by fractional distillation of caraway oil and spearmint oil, respectively. However, these carvones are now prepared synthetically, the preferred starting material being (+)- and (-)-limonenes, which are converted into the corresponding optically active carvones. Since optical rotation is reversed in the process, (+)-limonene is the starting material for (—)-carvone. 

Dihydromyrcene Manufacture. 2,6-Dimethyl-2,7-octadiene, commonly known as dihydromyrcene (24) or citronellene, is produced by the pyrolysis of pinane, which can be made by hydrogenation of a- or p-pinene (101). If the pinene starting material is optically active, the product is also optically active (102). The typical temperature for pyrolysis is about 550—600°C and the crude product contains about 50—60% citronellene. Efficient fractional distillation is required to produce an 87—90% citronellene product. 

Cyelopentene was dissolved in CCf,. Bromine was added to the solution at low temperatures and low light. The product tested negative for oprical activity. An optically active reagent was then added and, upon fractional distillation, two fractions were obtained. Each fraction was then precipitated and rinsed in an acid bath. The final products were found to have opposite observed rotations. 

The design of host compounds for optical resolution has received much attention. Toda [23,24] has reviewed the subject, and has used a number of novel techniques to effect efficient optical separation. He has demonstrated the possibility of resolving a racemic oil by stirring in a water suspension of a chiral host [25], and has applied fractional distillation techniques at different temperatures to separate a variety of racemic guests in the presence of chiral hosts [26]. An overview of the industrial applications and production of optically active materials is given in the book Chirality in Industry [27],... 

Optical Resolution by Inclusion Crystallization in Suspension Media and by Fractional Distillation... 

It was found that efficient inclusion crystallization can be accomplished simply by mixing powdered crystalline host and a hydrophobic guest compound in hexane or water. By using the inclusion crystallization in suspension media, very efficient optical resolution method was established. Furthermore, when inclusion complexation between chiral host and rac-guest in the solid state is combined with a distillation procedure, optical resolution can easily be accomplished by the fractional distillation procedure. 

Although some kinds of optically active compounds can be prepared by an asymmetric synthesis using a chiral catalyst, this method is not applicable for preparation of all kinds of compounds. Furthermore, optical yields of the product are not always very high. On the contrary, optical resolution method by inclusion complexation with a chiral host is applicable to various kinds of guest compounds as described in this chapter. When optically pure product cannot be obtained by one resolution procedure, perfect resolution can be accomplished by repeating the process, although asymmetric synthetic process cannot be repeated. Especially, optical resolutions by inclusion complexation with a chiral host in a water suspension medium and by fractional distillation in the presence of a chiral host are valuable as green and sustainable processes. 

Toda, F., and Tohi, Y. (1993) Novel Optical Resolution Methods by Inclusion Crystallisation in Suspension Media and by Fractional Distillation, J. Chem. Soc., Chem. Commun., 1238-1240. 

Cramer, F., and Dietsche, W. 378 (1959) Occlusion compounds. XV. Resolution of racemates with cyclodextrins, Chem. Ber. 92 b) Toda, F., and Tohi, Y. (1993) Novel optical resolution methods by inclusion crystallization in suspension media and by fractional distillation,/. Chem. Soc., Chem. Commun., 1238-1240 c) Toda, F., and Tanaka, K. (1988) A new chiral host compound... 

The optically active derivative I was founded in a mixture of d-, 1- and meso-forms. The cis-trans isomers of II could be separated by careful fractional distillation or by gas chromatography. The configuration of the chlorophenyl derivatives could be estimated by dipole measurements. The chlorine atoms were exchanged with hydrogen by Grignard reaction and hydrolysis, so the configuration of the phenyl compounds was also determined. The cis and trans forms differ in their physicochemical constants and in their NMR spectra. 

The identity of most physical properties of enantiomers has one consequence of great practical significance. They cannot be separated by ordinary methods not by fractional distillation, because their boiling points are identical not by fractional crystallization, because their solubilities in a given solvent are identical (unless the solvent is optically active) not by chromatography, because they are held equally strongly on a given adsorbent (unless it is optically active). The separation of a racemic modification into enantiomers—the resolution of a racemic modification—is therefore a special kind of job, and requires a special kind of approach (Sec. 7.9). 

To purify the 5ec-butyl chloride obtained by chlorination of n-butane, we would carry out a fractional distillation. But since the enantiomeric jcc-butyl chlorides have exactly the same boiling point, they cannot be separated, and are collected in the same distillation fraction. If recrystallization is attempted, there can again be no separation since their solubilities in every (optically inactive) solvent are identical. It is easy to see. then, that whenever a racemic modification is formed n a reaction, we will isolate (by ordinary methods) a racemic modification. 

P oUem 7.2 Isopentane is allowed to undergo free-radical chlorination, and the reaction mixture is separated by careful fractional distillation, (a) How many frac tions of formula CsHnCl would you expect to collect (b) Draw structural formulas, stereochemical where pertinent, for the compounds making up each fraction. Specify each enantiomer as R or S. (c) Which if any, of the fractions, as collected, would show optical activity (d) Account in detail—just as was done in the preceding section— for the optical activity or inactivity of each fraction. 

Problem 7.3 We carry out free-radical chlorination of (S)-Avr-butyl chloride, and by fractional distillation isolate the various isomeric products, (a) Draw stereochemical formulas of the 1,2-, 2,2-, and 1,3-dichlorobutanes obtained in this way. Give each enantiomer its proper R or S specification, (b) Which of these fractions, as isolated, will he optically active, and which will be optically inactive ... 

Problem 7.8 Each of the following reactions is carried out, and the products are separated by careful fractional distillation or recrystallization. For each reaction tell how many fractions w ill be collected. Draw stereochemical formulas of the compound or compounds making up each fraction, and give each its R/S specification. Tell whether each fraction, as collected, will show optical activity or optical inactivity. 

We know (Sec. 7.3) that when optically inactive reactants form a chiral compound, the product is the racemic modification. We know that the enantiomers making up a racemic modification have identical physical properties (except for direction of rotation of polarized light), and hence cannot be separated by the usual methods of fractional distillation or fractional crystallization. Yet throughout this book are frequent references to experiments carried out using-... 

By careful fractional distillation they separated the l,2-dichloro-2-methyl-butane from the reaction mixture, and found it to be optically inactive. From this they concluded that the mechanism involving free alkyl radicals, (2a), (3a), is the correct one. This mechanism is accepted without question today, and the work of Brown, Kharasch, and Chao is frequently referred to as evidence of the stereochemical behavior of free radicals, with the original significance of the work exactly reversed. 

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