Lithium - liquid ammonia

ALCOHOL represents a convenient method of converting allyl alcohol to 2-substituted 1-propanols, while a one-pot reaction sequence of alkylation (alkyl lithium) and reduction (lithium—liquid ammonia) provides excellent yields of AROMATIC HYDROCARBONS FROM AROMATIC KETONES AND ALDEHYDES. 

The irradiation of enone 20 in the presence of Et3N or DABCO as electron donors yields 21 as major product and almost none of the valence tautomerized product 22 (equation 29)139. Photomediated electron transfer apparently differs here from alternative electron transfer processes, since in lithium/liquid ammonia and electrochemical reductions 22 is produced. 

Reduction.—la,2a-Epoxycholesta-4,6-dien-3-one (63) has been reduced by lithium-liquid ammonia under strictly controlled conditions to give a mixture which included 45% of the la,3/3-dihydroxy-5a-6-ene (64), and 20% of the A5-isomer.88 The A6-compound was used in the preparation of la,3/3-dihydroxycholesta-5,7-diene, required for the synthesis of la-hydroxy-vitamin D3. 

Birch reduction of aryltrialkylsilanes by lithium-liquid ammonia-ethanol at -70 °C has been studied systematically and a typical conversion is indicated in Scheme 38. ° The major products are usually the... 

Yoneda, R., Osaki, H., Harusawa, S., and Kurihara, T., Reductive deoxygenation of a,P-unsatured ketones via cyanophosphates by lithium in liquid ammonia, Chem. Pharm. Bull., 37, 2817, 1989. Yoneda. R.. Osaki, T., Harusawa, S., and Kurihara, T., Dephosphorylation of cyano diethyl phosphates by reduction with lithium-liquid ammonia. An efficient method for conversion of carbonyl compounds into nitriles.. 1. Chem. Soc.. Perkin Trans. 1, 607, 1990. 

Reduction of amines. Birch13 noted that N,N-dimethylaniIines are reducible by lithium and liquid ammonia, but Stork and White14 made the more significant observation that the primary amine precursors of the tertiary amines are also reducible in satisfactory yields. In a careful study of the reduction of o-toluidine. the highest yields were obtained with the combination lithium-liquid ammonia-/-butanol. One advantage of using an amine as substrate is that the unreduced basic amine is readily separated from neutral ketonic products. In all cases examined the desired unsatura-... 

The indole ring system is not reduced by nucleophilic reducing agents, such as lithium aluminium hydride or sodium borohydride lithium/liquid ammonia does, however, reduce the benzene ring 4,7-dihydroindole is the main product. ... 

X = H2) with hydrobromic acid followed by esterification of the resulting diphenol with diethyl phosphite gave an intermediate diester which, upon lithium-liquid ammonia reduction, provided the trans-base (15 R = — H, X = H2). 

Lithium/liquid ammonia conditions can produce 1,4-dihydroquinoline and 3,4-dihydroisoquinoline under certain conditions. Conversely, lithium aluminium hydride reduces generating 1,2-dihydroquinoline and -isoquinoline. These dihydro-heterocycles can be easily oxidised back to the fully aromatic systems, or disproportionate, especially in acid solution, to give a mixture of tetrahydro- and aromatic compounds. 

CH3)2N]3P0. M.p. 4°C, b.p. 232"C, dielectric constant 30 at 25 C. Can be prepared from dimethylamine and phosphorus oxychloride. Used as an aprotic solvent, similar to liquid ammonia in solvent power but easier to handle. Solvent for organolithium compounds, Grignard reagents and the metals lithium, sodium and potassium (the latter metals give blue solutions). 

The stability of most acetylides, M-Ce8R, in organic solvents, even at room temperature or in liquid ammonia, allows a great variety of synthetic operations to be performed under different conditions (see inter alia refs. 1-5). Lithium... 

Anhydrous liquid ammonia (note 2) (900 ml) was drawn from a cylinder and introduced into the flask. Iron(III) nitrate (lOO mg) was added and, as soon as a uniformly brown solution had formed (after stirring for a few seconds), about 0.7 g of lithium (from the starting amount of 7 g) was cut into two or three pieces and immediately introduced into the flask. After 10-15 min the blue colour had disappeared completely and a white suspension of lithium amide had formed. The remainder of the 7 g (1 mol) of lithium was then cut up and introduced. In most cases the conversion was finished v/ithin about 30 min (note 3). 

In contrast to the reaction with lithium amide, the sodium amide suspension immediately settles out after stopping the stirring and the supernatant ammonia has a grey or black colour, due to colloidal iron. In some cases it took a long time before all of the sodium had been converted (note 4). A further 0.1 g of iron(III) nitrate was then added to accelerate the reaction and some liquid ammonia was introduced to compensate for the losses due to evaporation. 

The amount of metal required gives an indication of the water content. note 3. If the conversion takes longer, add some liquid ammonia to keep the volume of the suspension between 500 and 800 ml. iinte 4. The conversion of lithium and potassium into the alkali amides has never given problems. 

To a vigorously stirred suspension of 4 mol of lithium amide (see II, Exp. II) in 2.5 1 of liquid ammonia were added in 25 min 2 mol of propargyl alcohol (commercially available, purified before use by distillation at 100-120 mm). The suspension became very thin. Subsequently, the dropping funnel was combined with a gas inlet tube reaching about 1 cm beneath the surface of the ammonia. The vent on the splashing tube was removed. Methyl iodide (2 mol) was added to the vigorous-... 

Hove 1. The procedure described in Ref. 1 was modified. To a solution of 2.0 mol of lithium acetylide in 1.2 1 of liquid ammonia in a 4-1 round-bottomed, three-necked flask (see Fig. 2) was added 1.5 mol of freshly distilled benzaldehyde with cooling at about -45°C. After an additional 30 min finely powdered ammonium chloride (2 mol) was introduced in 15 min. The ammonia was allowed to evaporate, then water (1.1 1) was added and the product was extracted with diethyl ether. After drying over magnesium sulfate the extract was concentrated in a water-pump vacuum. High-vacuum distillation,... 

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 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). 

The Birch reductions of C C double bonds with alkali metals in liquid ammonia or amines obey other rules than do the catalytic hydrogenations (D. Caine, 1976). In these reactions regio- and stereoselectivities are mainly determined by the stabilities of the intermediate carbanions. If one reduces, for example, the a, -unsaturated decalone below with lithium, a dianion is formed, whereof three different conformations (A), (B), and (C) are conceivable. Conformation (A) is the most stable, because repulsion disfavors the cis-decalin system (B) and in (C) the conjugation of the dianion is interrupted. Thus, protonation yields the trans-decalone system (G. Stork, 1964B). 

A useful alternative to catalytic partial hydrogenation for converting alkynes to alkenes IS reduction by a Group I metal (lithium sodium or potassium) m liquid ammonia The unique feature of metal-ammonia reduction is that it converts alkynes to trans alkenes whereas catalytic hydrogenation yields cis alkenes Thus from the same alkyne one can prepare either a cis or a trans alkene by choosing the appropriate reaction conditions... 

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