Lithium acidic hydrocarbons

Obviously, only noimucleophilic bases can be employed for the formation of enolates from carbonyl and carboxyl compounds. A base is nonnucleophilic if it is very bulky. The only nonnucleophilic organolithium compounds that deprotonate carbonyl and carboxyl compounds are mesityllithium (2,4,6-trimethylphenyllithium) and trityl-lithium (triphenylmethyllithium). However, these bases do not have any significance for the generation of enolates because of the difficulties associated with their preparation and with the separation of their conjugate acid hydrocarbons. 

An electropositive metal in organic compounds of alkali metals is replaced by a more electropositive one in series of reversible reactions. More electronegative, i. e. more acid, hydrocarbon groups or whole molecules replace those which are less acid [140]. Caesium replaces lithium in ethyllithium. Benzene, which is a stronger acid than ethane, replaces ethyl in ethyllithium. Toluene and H2 are more acid than benzene, and they can therefore replace phenyl in phenylsodium [141, 142],... 

Lithium metal may react with acidic hydrocarbons to give organolithiums. This reaction also occurs with other alkali metals, more commonly with the heavier group-IA metals potassium and Cs (see 5.5.3.2.4). Usually, deprotonation of acidic hydrocarbons ( 5.5.2.3.2) is the method of choice for organolithiums from acidic hydrocarbons, but in special cases where contaminants must be avoided, the direct reaction with Li metal can be useful. 

Table 1. Organolithiums from Lithium Metal with Acidic Hydrocarbons ...

Lithium arene radical anions and dianions, [ArH2] Li and [ArH] 2 Li", can react with acidic hydrocarbons , alkyl halides or alkyl sulfides to form organolithiums via electron transfers. 

Acidic hydrocarbons such as alkynes or cyclopentadienes can be metallated with butyl-lithium. For less acidic hydrocarbons, the nucleophilicity has to be enhanced with a ligand such as TMEDA or potassium t-butoxide... 

Estrone, a key intermediate in the preparation of medicinally useful 19-norsteroids, can now be prepared in high yield at the remarkably low temperature of 35° from A -androstadiene-3,17-dione 17-ethyleneketal (1) by reaction with lithium-diphenyl in THF in the presence of a suitably acidic hydrocarbon such as diphenyl-methane to intercept the by-product methyllithium and prevent its addition to the potential 17-carbonyl group. ... 

In the absence of more acidic hydrocarbons, ethylene serves as both telogen and taxogen. The addition of ethylene to the lithium-carbon bond was previously observed by Ziegler, et al. (16). Those authors also found that ether catalyzes the addition reaction. However only growth products such as hexyl-, octyl-, and decyllithium were formed. 

From this value and known C—H bond dissociation energies, pK values can be calculated. The electrochemical measurements can be made on halides or on alkyl-lithium compounds. This type of approach has some significant uncertainties but nevertheless can provide a least a semiquantitative estimate of acidities of very weakly acidic hydrocarbons. The pK for isobutane obtained in this way is 71. The necessary electrochemical measurements cannot be made directly for methane, but an extrapolation from toluene and diphenylmethane leads to a range of 52-62 for the pK of methane. ... 

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). 

From the time that isoprene was isolated from the pyrolysis products of natural mbber (1), scientific researchers have been attempting to reverse the process. In 1879, Bouchardat prepared a synthetic mbbery product by treating isoprene with hydrochloric acid (2). It was not until 1954—1955 that methods were found to prepare a high i i -polyisoprene which dupHcates the stmcture of natural mbber. In one method (3,4) a Ziegler-type catalyst of tri alkyl aluminum and titanium tetrachloride was used to polymerize isoprene in an air-free, moisture-free hydrocarbon solvent to an all i7j -l,4-polyisoprene. A polyisoprene with 90% 1,4-units was synthesized with lithium catalysts as early as 1949 (5). 

The equihbrium shown in equation 3 normally ties far to the left. Usually the water formed is removed by azeotropic distillation with excess alcohol or a suitable azeotroping solvent such as benzene, toluene, or various petroleum distillate fractions. The procedure used depends on the specific ester desired. Preparation of methyl borate and ethyl borate is compHcated by the formation of low boiling azeotropes (Table 1) which are the lowest boiling constituents in these systems. Consequently, the ester—alcohol azeotrope must be prepared and then separated in another step. Some of the methods that have been used to separate methyl borate from the azeotrope are extraction with sulfuric acid and distillation of the enriched phase (18), treatment with calcium chloride or lithium chloride (19,20), washing with a hydrocarbon and distillation (21), fractional distillation at 709 kPa (7 atmospheres) (22), and addition of a third component that will form a low boiling methanol azeotrope (23). 

Robertson et al.261 measured rates of bromination of some aromatic hydrocarbons in acetic acid containing sodium acetate (to eliminate protonation of the aromatic by liberated hydrogen bromide) and lithium bromide (to reduce the rate to a measurable velocity ) at 25 °C, the second-order rate coefficients for 3-nitro-N,N-dimethylaniline and anisole being 14.2 and 0.016 respectively the former compound was thus stated to be about 1012 times as reactive as benzene (though no measurement of the latter rate coefficient, inferred to be 1.33 xlO-11, could be found in the literature) and this large rate spread gives one further indication of the unreactive nature of the electrophile. Other rates relative to benzene were ... 

Acetone Acetylene Alkali and alkaline earth metals, e.g. sodium, potassium, lithium, magnesium, calcium, powdered aluminium Anhydrous ammonia Concentrated nitric and sulphuric acid mixtures Chlorine, bromine, copper, silver, flourine or mercury Carbon dioxide, carbon tetrachloride, or other chlorinated hydrocarbons. (Also prohibit, water, foam and dry chemical on fires involving these metals - dry sand should be available.) Mercury, chlorine, calcium hypochlorite, iodine, bromine or hydrogen fluoride... 

Although lithium aluminium hydride does not reduce alkenes or acetylene hydrocarbons, it reduces allylic alcohols and their acetylenic counterparts. Thus cinnamic acid is reduced to dihydrocinnamyl alcohol. 

Formally related reactions are observed when anthracene [210] or arylole-fines [211-213] are reduced in the presence of carboxylic acid derivatives such as anhydrides, esters, amides, or nitriles. Under these conditions, mono- or diacylated compounds are obtained. It is interesting to note that the yield of acylated products largely depends on the counterion of the reduced hydrocarbon species. It is especially high when lithium is used, which is supposed to prevent hydrodimerization of the carboxylic acid by ion-pair formation. In contrast to alkylation, acylation is assumed to prefer an Sn2 mechanism. However, it is not clear if the radical anion or the dianion are the reactive species. The addition of nitriles is usually followed by hydrolysis of the resulting ketimines [211-213]. 

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