Lithium Amide in Liquid Ammonia

Apparatus 21 round-bottomed flask (three vertical necks), equipped with a mechanical stirrer, a gas-outlet (curved glass tube, 5 mm internal diameter, with glass joint). A stopper is placed on the third neck. 

The plastic tube may contain some moisture. It is therefore advisable to rinse the tube a few seconds with the stream of liquid ammonia, before the end of the tube is placed into the reaction flask. 

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Electron-transfer initiation from other radical-anions, such as those formed by reaction of sodium with nonenolizable ketones, azomthines, nitriles, azo and azoxy compounds, has also been studied. In addition to radical-anions, initiation by electron transfer has been observed when one uses certain alkali metals in liquid ammonia. Polymerizations initiated by alkali metals in liquid ammonia proceed by two different mechanisms. In some systems, such as the polymerizations of styrene and methacrylonitrile by potassium, the initiation is due to amide ion formed in the system [Overberger et al., I960]. Such polymerizations are analogous to those initiated by alkali amides. Polymerization in other systems cannot be due to amide ion. Thus, polymerization of methacrylonitrile by lithium in liquid ammonia proceeds at a much faster rate than that initiated by lithium amide in liquid ammonia [Overberger et al., 1959]. The mechanism of polymerization is considered to involve the formation of a solvated electron ... 

Dioxepins derived from 1,4-diols and a-phenylsulfonylacetaldehyde diethyl acetal have proved to be robust protection groups for 1,4-diols under a variety of reaction conditions. They are stable to 60% AcOH, 6M HC1, and 0.1 M H2SC>4, and they resist /3-elimination by reaction with l,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Cleavage was achieved with either lithium amide in liquid ammonia at —33 °C or -butyllithium at 35 °C (Scheme 24) <2003SC895>. 

A similar synthesis of enantiopure (l )-sulfinamides 123 from indane-derived toluenesulfonyl 1,2,3-oxathiazolidine-2-oxide 121 has been developed. This method includes chemoselective ring opening with inversion of configuration at the sulfur atom, using Grignard reagent at the first step and lithium amide in liquid ammonia in the second step (Scheme 17) <2002JA7880>. Intermediate stable and crystalline sulfinate esters 122 were isolated in >95% yield in diastereopure form. 

Lithium amide in liquid ammonia has been as successful as sodium amide in inducing dehydrohalogenation of dihaloalkyl ethers and halovinyl ethers to 1-alkynyl ethers . Lithium dialkylamides have also found use in the preparation of aryl- and alkylacetylenes in high yields , and of protected acetylenic sugars . They have also been utilized for concurrent elimination and substitution in the synthesis of ynamines , obtained in 30-40% overall yield from the corresponding aldehydes... 

A useful technique to accomplish overall vicinal dialkylation of enones is to trap the enolate initially formed in the conjugate addition with TMS-Cl, and then regenerate the enolate under suitable conditions for its alkylation. Lithium 1-enolates of 3,5-dialkylcyclohexanones generated from the reaction of the corresponding TMS enol ethers with lithium amide in liquid ammonia-THF can be alkylated efficiently in liquid ammonia-THF, even with an unreactive alkylating agent such as n-butyl iodide (Scheme 10). ... 

Patterson and Fried found that the clean lithium enolate (14), generated by conjugate addition of the lithium divinylcuprate (15) to cyclopentenone with subsequent trapping of the initial enolate with TMS-Cl and cleavage of the TMS enol ether with lithium amide in liquid ammonia-THF, could be alkylated in a reasonable yield with the (Z)-allylic iodide (16) to give the 11-deoxyprostaglandin derivative (17 ... 

Phe reagent can be prepared in situ by treating / -chIorovinyl ethyl ether with lithium amide in liquid ammonia and used in the synthesis of ethoxyethynylcarbmols of type (1). This substance (1) is convertible by selective hydrogenation (Lindlar... 

Less hindered bases can be used to form the enolate, provided tertiary butyl esters are employed to retard reactions at the carbonyl group. For example, lithium amide in liquid ammonia has been successfully used for the alkylation of f-butyl acetate. 

Miscellaneous Substitutions.— The enhanced reactivity of the 2-methyl group in thiazole is illustrated by the hydroxyalkylation of 2,4-dimcthyl-thiazole to the alcohols (62), on successive treatment with lithium amide in liquid ammonia, and with a carbonyl compound the products are readily dehydrated to the ethylenes (63). ... 

Synthesis of Sulfinamides. The nucleophilic substitution of chiral enantiopure sulfinate esters with NaHMDS led to S-O bond breakage with inversion of configuration at the S atom, giving quantitative conversion to chiral sulfinamides (eq 10). Lithium amide in liquid ammonia at —78°C could be also used, although in some cases such as in the synthesis of (/ )-(+)-p-toluenesulfinamide higher ee s were observed when using NaHMDS. ... 

Compounds of the general formula (R3Sn)3N have also been prepared by Sisido and Kozima (78) who used trialkyltin halides and lithium amide (in liquid ammonia, ether, or tetrahydrofuran) or sodamide (in liquid ammonia). 3RsSnX + 3MNH2 (R3Sn)3N+3MX+2NHs... 

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