Liquid ammonia techniques

Many important synthetic organic reactions are carried out in liquid ammonia (b.p. — 33 °C) this is a good solvent for many organic compounds having a 

Solutions of these metals in liquid ammonia effect (i) the reduction of a range of functional groups such as carbonyl and acetylenic and also conjugated and aromatic systems, and (ii) cleavage of benzyl and allyl ethers and thioethers. These reactions are usually carried out by the general procedure of adding the metal to a solution of the substrate in liquid ammonia to which dry methanol or ethanol or t-butanol has been added to provide a ready proton source (alcohols are more acidic than ammonia).34 

A second principal use of liquid ammonia involves forming a suspension of an alkali metal amide (LiNH2, KNH2 or NaNH2) by adding the appropriate metal to liquid ammonia containing a trace of iron(m) ions (added as iron(m) nitrate) as a catalyst. 

The amide ions are powerful bases and may be used (i) to dehydrohalogenate halo-compounds to alkenes and alkynes, and (ii) to generate reactive anions from terminal acetylenes, and compounds having reactive a-hydrogens (e.g. carbonyl compounds, nitriles, 2-alkylpyridines, etc.) these anions may then be used in a variety of synthetic procedures, e.g. alkylations, reactions with carbonyl components, etc. A further use of the metal amides in liquid ammonia is the formation of other important bases such as sodium triphenylmethide (from sodamide and triphenylmethane). 

Although these amides are frequently used as a suspension in liquid ammonia, an inert co-solvent (such as ether or tetrahydrofuran) may be added should the organic substrate not be readily soluble in liquid ammonia. Alternatively after amide formation the liquid ammonia may be allowed to evaporate completely during simultaneous addition of the inert solvent subsequently the organic substrate may be added in the same solvent to the alkali amide. 

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Freudenberg was able to prepare fully methylated a- and /3-dextrins. The starting materials, particularly the a-dextrin, were probably of higher purity than those used by Irvine and Pringsheim. Besides, Freudenberg applied the Muskat liquid ammonia technique to the methylation, which... 

Since the first preparation of alkali-metal intercalates by the liquid ammonia technique, many preparation methods have been proposed. The most commonly used fall into four main groups (i) use of alkali-metal solutions in liquid ammonia, (ii) use of organometallic reagents, (iii) solid-state techniques and (iv) electrochemical processes. 

A solvent of much greater versatility for the preparation of sodium derivatives of carbohydrates is liquid ammonia. Schmid and Becker (16) showed that the liquid ammonia technique could be used to prepare sodium derivatives of carbohydrates. Muskat prepared the sodium derivatives of sugars after removal of the liquid ammonia, the products were resuspended in an inert solvent and alkylated with methyl iodide. Potassium and lithium derivatives also were made by Muskat (17),... 

By applying new vacuum line technology to liquid ammonia techniques, one can carry out clean high-yield syntheses of pentamethylcyclopentadienyl europium(II) and ytterbium(II) complexes from the respective metals (Wayda et al., 1984). The authors concluded that their reaction conditions produced genuinely stable metal-ammonia solutions, although the behavior of the two lanthanides differed in one particular aspect while there was no evidence for an isolable EU-NH3 bond, it was possible to prepare and characterize an unusual ytterbium complex coordinated to both a THF moiety and an ammonia molecule. 

Sulfur dissolves in liquid ammonia to give intensely coloured solutions. The colour is concentration-dependent and the solutions are photosensitive.Extensive studies of this system by several groups using a variety of spectroscopic techniques, primarily Raman,... 

Evidence for symmetrical intermediates such as benzyne cannot be established by quantitative analysis of the reaction mixture unless a labelled starting substance is used. By applying labeling techniques, Roberts and his collaborators obtained results which indicated that benzyne (13) occurs as an intermediate in the amination of chlorobenzene with potassium amide in liquid ammonia. From chlorobenzene-1-C (12) about equal amounts of anUine-l-C (14) and aniline-2-C (15) were formed. More or less probable alternative... 

Polytetrafluorethylene (p.t.f.e.) This polymer does not absorb water, has no solvents and is almost completely inert to chemical attack molten alkali metals and sodium in liquid ammonia are the rare exceptions. Furthermore it does not soften below 320°C, is electrically inert and has a very low coefficient of friction. It is more expensive than general purpose plastics, requires special fabrication techniques, is degraded by high energy radiation, and has a low creep resistance. 

Solutions of alkali metals in liquid ammonia have been studied by many techniques. These include electrical conductivity, magnetic susceptibility, nuclear magnetic resonance (NMR), volume expansion, spectroscopy (visible and infrared), and other techniques. The data obtained indicate that the metals dissolve with ionization and that the metal ion and electron are solvated. Several simultaneous equilibria have been postulated to explain the unique properties of the solutions. These are generally represented as follows ... 

One of the most common techniques for preparing Zintl phases is by the reaction of a solution of the alkali metal in liquid ammonia with the other element. However, many of these materials are obtained by heating the elements. For example, heating barium with arsenic leads to the reaction... 

The ENDOR technique refers to electron-nuclear double resonance. This consists of the effect on a partially saturated ESR line of simultaneously irradiating the sample with a radiofrequency to induce nuclear resonance transitions of hyperfine coupled nuclei. It may enable one to obtain information about signs of coupling constants. ELDOR is the technique corresponding to electron-electron double resonance. Such techniques, coupled with TRIPLE resonance, have been utilized and well described in a discussion of pyridine and 4,4-bipyridyl radical anion ESR spectra measured in sodium/liquid ammonia (80JMR<41)17). 

The main methods of reducing ketones to alcohols are (a) use of complex metal hydrides (b) use of alkali metals in alcohols or liquid ammonia or amines 221 (c) catalytic hydrogenation 14,217 (d) Meerwein-Ponndorf reduction.169,249 The reduction of organic compounds by complex metal hydrides, first reported in 1947,174 is a widely used technique. This chapter reviews first the main metal hydride reagents, their reactivities towards various functional groups and the conditions under which they are used to reduce ketones. The reduction of ketones by hydrides is then discussed under the headings of mechanism and stereochemistry, reduction of unsaturated ketones, and stereochemistry and selectivity of reduction of steroidal ketones. Finally reductions with the mixed hydride reagent of lithium aluminum hydride and aluminum chloride, with diborane and with iridium complexes, are briefly described. 

An anionic technique by indirect grafting was proposed for N-metallation of Nylon by Yamaguchi (153-155), in which alcali metals dissolved in liquid ammonia displace the amidic hydrogen atoms. Nylon derivatives and graft copolymers can be synthetized from the N-metallated Nylon (153). For ethylene oxide as grafting monomer, the metallated fibers were soaked in a tetrahydro-furan solution of the monomer, at 60° C (154). Methyl methacrylate is grafted on Nylon with a conversion over 90% by this technique (155). Other procedures involve the use of sodium methoxide in methanol solution and subsequent anionic graft copolymerization of acrylonitrile in a tetrahydrofuran solution (156). 

The principles underlying the N- alkylation of indoles are the same as those for pyrroles (67T3771). Development of synthetic techniques for maximizing yields has resulted in procedures using dipolar aprotic solvents, crown ether and phase transfer catalysis, as well as reactions in liquid ammonia. These techniques are illustrated by some representative examples given in Table 8. 

B. Sealed Tube Preparations. Sealed tube reactions and purifications afford good exclusion of the atmosphere and permit operations at moderate pressures. The latter capability makes it possible to work with highly volatile solvents, such as liquid ammonia, at room temperature. Since the sealed tube is often loaded on a high-vacuum line, the details on these techniques are given in Chapter 9. 

Alkali and alkaline earth metals dissolve in liquid ammonia with the formation of solvated electrons. These solvated electrons constitute a very powerful reducing agent and permit reduction of numerous conjugated multiple-bond systems. The technique, named for Birch provides selective access to 1,4-cydohcxiidicnes from substituted aromatics.8 In the case of structures like 21 that are substituted with electron-donating groups, electron transfer produces a radical anion (here 22) such that subsequent protonation occurs se lectively in the ortho position (cf intermediate 23) A second electron-transfer step followed by another protonation leads to com pound 24... 

CAUTION This experiment must be conducted in an efficient fume cupboard and the precautions and techniques for handling liquid ammonia described in Section 2.17.7, p. 116, must be noted. 

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