Lithium acids

In 1821 Arfwedson published a supplementary note to his lithium research (11), in which he stated that the salt which he had previously reported as lithium acid sulfate must be the normal sulfate and that the double sulfate he had at first taken for lithium alum was really potassium alum resulting from a trace of potassium in his alumina. 

Formylcyclohex-2-enones are available from 3-alkoxycyclohex-2-enones by reaction with bis(methylthio)methyl-lithium, acid-catalysed hydrolysis, and de-thioketalization (Scheme 69). 

Lithium hydroxide with 12-hydroxy-stearic acid (or hydrogenated castor oil) they form the family of lithium greases very commonly used for general lubrication and bearing lubrication. 

When hydrogen sulphide is bubbled into an acidic solution of an antimony or a bismuth salt an orange precipitate, SbjSs, or a brown precipitate, BijS, is obtained. Bismuth(III) sulphide, unlike antimony(IIl) sulphide, is insoluble in lithium hydroxide. 

Lithium aluminium hydride, LiAlH, is a very active reducing agent, and is used particularly for the ready reduction of carboxylic acids (or their esters) to primary alcohols R-COOH -> R CH,OH. 

Required Salicylic acid, 6 0 g. lithium aluminium hydride, 2 5 g. dry ether, 165 ml. 

Thus o-hydroxyphenyl-llthium cannot be obtained from o-bromophenol and lithium but, under proper conditions, o-bromophenol reacts with n-butyl-lithium to give a good yield of the lithium salt of o-hydroxyphenyl-hthium. An interesting application is to the preparation from m-bromochlorobenzene and M-butyl-lithlum of w-chlorobenzoic acid—an expensive chemical ... 

For initial experience in the uae of Uthium, the preparation of either p-toluic acid or of a-napbtboic acid mcay be undertaken. For the former, p-bromotoluene is converted into the lithium derivative and the latter carbonated with soUd carbon dioxide ... 

Some di-p-tolyl ketone is produced as a by-product, presumably by Interaction of the lithium salt of the carboxylic acid with the aryl lithium ... 

The kinetics of the nitration of benzene, toluene and mesitylene in mixtures prepared from nitric acid and acetic anhydride have been studied by Hartshorn and Thompson. Under zeroth order conditions, the dependence of the rate of nitration of mesitylene on the stoichiometric concentrations of nitric acid, acetic acid and lithium nitrate were found to be as described in section 5.3.5. When the conditions were such that the rate depended upon the first power of the concentration of the aromatic substrate, the first order rate constant was found to vary with the stoichiometric concentration of nitric acid as shown on the graph below. An approximately third order dependence on this quantity was found with mesitylene and toluene, but with benzene, increasing the stoichiometric concentration of nitric acid caused a change to an approximately second order dependence. Relative reactivities, however, were found to be insensitive... 

To absolution of 1.00 mol of ethyl lithium in 800-900 ml of diethyl ether (see Chapter II, Exp. 1) was added, with cooling between -20 and -10°C, 0.50 nol of dry propargyl alcohol, dissolved in 100 ml of diethyl ether. Subsequently 1.1 mol of trimethylchlorosilane was introduced over a period of 25 min with cooling between -15 and +5°C. After stirring for an additional 2 h at about 30°C the suspension was poured into a solution of 30 g of acetic acid in 150 ml of water. After stirring for 1 h at room temperature the layers were separated and the aqueous layer v/as extracted four times with diethyl ether. The combined ethereal solutions were washed with sodium hydrogen carbonate solution in order to neutralize acetic acid, and were then dried over magnesium sulfate. The diethyl ether was removed by evaporation in a water-pump vacuum and the residue distilled... 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

The ketone is added to a large excess of a strong base at low temperature, usually LDA in THF at -78 °C. The more acidic and less sterically hindered proton is removed in a kineti-cally controlled reaction. The equilibrium with a thermodynamically more stable enolate (generally the one which is more stabilized by substituents) is only reached very slowly (H.O. House, 1977), and the kinetic enolates may be trapped and isolated as silyl enol ethers (J.K. Rasmussen, 1977 H.O. House, 1969). If, on the other hand, a weak acid is added to the solution, e.g. an excess of the non-ionized ketone or a non-nucleophilic alcohol such as cert-butanol, then the tautomeric enolate is preferentially formed (stabilized mostly by hyperconjugation effects). The rate of approach to equilibrium is particularly slow with lithium as the counterion and much faster with potassium or sodium. 

The most general synthetic route to ketones uses the reaction of carboxylic acids (or their derivatives) or nitriles with organometallic compounds (M.J. Jorgenson, 1970). Lithium car-boxylates react with organolithium compounds to give stable gem-diolates, which are decom-... 

The conversion of carboxylic acid derivatives (halides, esters and lactones, tertiary amides and lactams, nitriles) into aldehydes can be achieved with bulky aluminum hydrides (e.g. DIBAL = diisobutylaluminum hydride, lithium trialkoxyalanates). Simple addition of three equivalents of an alcohol to LiAlH, in THF solution produces those deactivated and selective reagents, e.g. lithium triisopropoxyalanate, LiAlH(OPr )j (J. Malek, 1972). 

The less hindered f/ans-olefins may be obtained by reduction with lithium or sodium metal in liquid ammonia or amine solvents (Birch reduction). This reagent, however, attacks most polar functional groups (except for carboxylic acids R.E.A. Dear, 1963 J. Fried, 1968), and their protection is necessary (see section 2.6). 

J. Rebek, Jr., (1987) first developed a new synthesis of Kemp s acid and then extensively explored its application in model studies. The synthesis involves the straightforward hydrogenation (A. Steitz, 1968), esterification and methylation of inexpensive 1,3,5-benzenetricar-boxylic acid (trimesic acid 30/100 g). The methylation of the trimethyl ester with dimethyl sulfate, mediated by lithium diisopropylamide (V. J. Shiner, 1981), produced mainly the desired aff-cis-1,3,5-trimethyl isomer, which was saponified to give Kemp s acid. 

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