Liquid ammonia carbonyl substitution

The Group VI metals would not be expected to form binary metal carbonyl cations, but they do form some substituted cations with nitrogen and phosphorus ligands. The paramagnetic monomeric and dimeric chromium pentacarbonyl iodides react in liquid ammonia with iodide expulsion. 

Rather less common are condensations between a-hydroxyketones, ammonia and an imidate. Equivalent amounts of the hydrochloride salt of the imidate and the or-substituted carbonyl compound (cr-halogeno-and a-acetoxyketones also take part) are heated (40-70°C) in liquid ammonia (3-48 h) at elevated pressures. Yields of imidazoles vary between 10 and 90%, but the requirements of working with liquid anomonia in an autoclave may make this approach unappealing if alternatives are available [42,43]. Examples include 4-hydroxymethyl- (35%), 4-hydroxymethyl-2-phenyl- (73%), 4-hydroxymethyl-2-(p-tolyl)- (68%) and 2-benzyl-4-hydroxymethylimidazoles (85%) [44]. 

The first report on the reduction of a carbonyl substituted cyclopropane was published in 1949. Reactions of methyl cyclopropyl ketone (131) with sodium in liquid ammonia in the presence of ammonium sulfate yielded instead of the expected methyl cyclopropylcarbinol (132) only a mixture of 2-pentanone (133) and 2-pentanol (134). 

Dimethyl-4,8-dioxaspiro[2.5]oct-l-ene is a synthetically useful precursor for cyclopropenones because of its stability and ready availability. The sodium derivative 1 of the cyclopropenone acetal in liquid ammonia reacted with alkyl halides giving alkyl-substituted cyclopropenone acetals 3. The lithiated cyclopropenone acetal 4 was generated by treating the cyclopropenone acetal with one equivalent of butyllithium in tetrahydrofuran. Reaction of the lithium carbanion 4 with alkyl halides proceeded cleanly in the presence of two equivalents of hexamethylphosphoric triamide (Table 1, entries 1-4). The lithium compound underwent nucleophilic addition to carbonyl compounds smoothly at — 70 C giving hydroxymethyl derivatives 5 (Table 1, entries 5-10). 

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). ... 

Ji et al. (2010,2012) discuss a number of types of reactions of organic substances in liquid ammonia, and provide many references to recent and earlier work. They compare the equilibrium constants of phenols and carbonyl-activated carbon adds in ammonia and water, and describe work that is part of an ongoing study of the kinetics of a variety of reactions, including aromatic substitutions and solvolyses in ammonia. They point out that owing to its weakness as an add and as a hydrogen-bond donor, in many respects ammonia behaves as a dipolar aprotic solvent. It solvates cations strongly, but anions hardly at all (Marcus, 1983,1985). The low value of the autoprotolysis constant ( 10 at -33°C) is chiefly due to the weakness of ammonia as an acid. The mobility of the NH ion in liquid ammonia is not anomalous (Lagowski,... 

Syntheses of Imidazoles with Liquid Ammonia. 6. N-Snhstituted Imidazoles. Stoeck,V. Schu-nack, W. (Fach-bereich Pharm., Univ. Mainz, Mainz, Ger ). Arch. Pharm. (Weinheim, Ger.) 1975, 308 (1), 72 (Ger.). N-Substituted imidazoles cannot be prepd. by reaction of imino esters and a-substituted carbonyl compds. in liq. NH3 as shown by reaction of benzoin with PhCH2NH2 in the presence or absence of PhC(OEt) NH HCl to give < 25% lophine (I). 

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