Deprotonation, in liquid ammonia

The use of sodium amide proved to be very successful in the synthesis of nonstabilized ylides free from lithium salts. - The reaction is usually carried out in liquid ammonia, but also a suspension of sodium amide in benzene or THF can be used. Whereas alkyltriarylphosphonium salts are deprotonated in liquid ammonia, in the case of the corresponding tetraalkyl compounds boiling THF is necessary. Mixtures of dry phosphonium salt and powdered sodium amide can be stored indefinitely and hence provide instant ylide mixtures. Upon addition of an ethereal solvent the ylide is quantitatively generated. 

Taking H3BO3 for example, which is a very weak acid in aqueous solutions (i.e., its grade of deprotonation is very low) becomes strongly deprotonated in liquid ammonia and is acting in reactions accordingly in such media. On the other hand, strong bases will loose... 

The most ionic of the organometallic derivatives of Group 1 elements are the acetylides and dicarbides formed by the deprotonation of alkynes in liquid ammonia solutions ... 

Herrmann et al. reported for the first time in 1996 the use of chiral NHC complexes in asymmetric hydrosilylation [12]. An achiral version of this reaction with diaminocarbene rhodium complexes was previously reported by Lappert et al. in 1984 [40]. The Rh(I) complexes 53a-b were obtained in 71-79% yield by reaction of the free chiral carbene with 0.5 equiv of [Rh(cod)Cl]2 in THF (Scheme 30). The carbene was not isolated but generated in solution by deprotonation of the corresponding imidazolium salt by sodium hydride in liquid ammonia and THF at - 33 °C. The rhodium complexes 53 are stable in air both as a solid and in solution, and their thermal stability is also remarkable. The hydrosilylation of acetophenone in the presence of 1% mol of catalyst 53b gave almost quantitative conversions and optical inductions up to 32%. These complexes are active in hydrosilylation without an induction period even at low temperatures (- 34 °C). The optical induction is clearly temperature-dependent it decreases at higher temperatures. No significant solvent dependence could be observed. In spite of moderate ee values, this first report on asymmetric hydrosilylation demonstrated the advantage of such rhodium carbene complexes in terms of stability. No dissociation of the ligand was observed in the course of the reaction. 

A type of deprotonation reaction that takes place in liquid ammonia but not in water occurs because it is possible to utilize the base strength of the amide ion. The reaction involves removing H+ from a molecule of ethylenediamine, H2NCH2CH2NH2 (written as en), that is coordinated to Pt2+ in the complex [Pt(en)2]2+. 

In the case of mono-ester substituted pyrroles (e.g., 68) wherein relatively unstable dianions likely to deprotonate ammonia might be produced, the authors instead utilized an excess of (MeOCH2CH2)2NH as a substitute for ammonia. It was felt that upon in situ formation of (MeOCH2CH2)2NLi, this base would be unable to protonate the dianion <00TL1331>. Remarkably, quenching the reduction reactions with benzoyl chloride affords P-keto esters (e.g., 69, R = COPh), a reaction that does not occur when conducted in liquid ammonia. 

Carbazole will react with 1 or 2 mol of ferrocene in hot decalin in the presence of aluminium-aluminium chloride producing crystalline derivatives in which either one or both" of the benzene rings is linked to iron, 25 and 26, respectively. The sandwich compound 25 was deprotonated to 27 with sodamide in liquid ammonia. A chromium carbonyl complex 28... 

The use of strong bases such as sodamide in liquid ammonia, lithium diisopropylamide and the alkyl- and aryl-lithiums gives essentially quantitative deprotonation at a side-chain alkyl group. The carbanions produced can undergo reactions with a wide range of electrophiles, as exemplified in Scheme 55. 

Even with lithium- or sodium amide in liquid ammonia, specific deproton anon at the ethynyl group is expected, but in this polar solvent subsequent nucleophilic substitution of Br ... 

Addition of a 2-alkynoic acid to alkali amide in liquid ammonia initially gives a solution of the alkali salt of the carboxylic acid. If an excess of alkali amide is present, the weakly basic salt is further deprotonated at a position next to the triple bond 183], This double deprotonation which may be compared with the formation of di-anions from 1,3-diketones and alkali amides [71], is essentially complete. The high kinetic stability of the alkynoic acid-dianion may be explained on the basis of resonance stabilization ... 

The chiral, nonracemic, tricyclic dioxopiperazine derivative 1, easily obtained from proline, is transformed with sodium amide in liquid ammonia into its monoenolate, then alkylated with bromoethane to give the chiral, nonracemic ethylation product 2. On deprotonation and further alkylation. 2 furnishes the achiral fra/w-dialkylated product 3 in good yield1. 

Different synthetic routes have been used to prepare these carbenes (Scheme 8.6). The most common procedure is the deprotonation of the conjugate acid. In early experiments, sodium or potassium hydride, in the presence of catalytic amounts of either f-BuOK or the DMSO anion were used. ° Then, Herrmann et al. showed that the deprotonation occurs much more quickly in liquid ammonia as solvent (homogeneous phase), and many carbenes of type IV have been prepared following this procedure. In 1993, Kuhn and Kratz" developed a new and versatile approach to the alkyl-substituted N-heterocyclic carbenes IV. This original synthetic strategy relied on the reduction of imidazol-2(3//)-thiones with potassium in boiling tetrahydrofuran (THF). Lastly, Enders et al." reported in 1995 that the 1,2,4-triazol-5-ylidene (Vila) could be obtained in quantitative yield from the corresponding 5-methoxy-l,3,4-triphenyl-4,5-dihydro-l//-l,2,4-triazole by thermal elimination (80 °C) of methanol in vacuo (0.1 mbar). 

The synthesis of sodium amide, NaNH2 (or sodamide ), by passing ammonia over heated sodium metal, was first reported almost two centuries ago. A number of studies have since been made of its properties, but no crystal structure has been reported. Sodamide is used as a strong base in organic chemistry (often in liquid ammonia solution). In contrast, sodium bis(trimethylsilyl)amide NaN(SiMe3)2 (or sodium hex-amethyldisilazide , NaHMDS), whose crystal structure is discussed later, is widely used for deprotonation reactions or base catalysed reactions due to its solubility in a wide range of non-polar solvents. An overview of some of the types of chemical reactions in which NaHMDS is used is presented in Scheme 2.3. 

In liquid ammonia, where the solvent is a much stronger base than water, the rate limiting deprotonation reactions can lead to some unusual rate laws. Because the solvent itself can act as a base, it is necessary to introduce an extra step in the reaction sequence discussed above, i.e. 

These principles apply to any solvent (Fig. 10.16) an acid is strong if its conjugate base is a weaker proton acceptor than the solvent. In such a case, the tug-of-war for the proton is resolved in favor of the solvent, so the acid is completely deprotonated. The acetate ion, CH3C02, is a weaker proton acceptor than an NH3 molecule, so acetic acid is a strong acid in liquid ammonia. A base is strong if it has a greater proton-pulling power than the solvent if the opposite is true, the base is weak. 

TV-Alkylation. 1-Substitution is favored when the indole ring is deprotonated and the reaction medium promotes the nudeophilicity of the resulting indole anion. Conditions which typically result in N-alkylation are generation of the sodium salt by sodium amide in liquid ammonia, use of sodium hydride or a similar strong base in IV,IV-dimethylformamide or dimethyl sulfoxide, or the use of phase-transfer conditions. 

The trifluoromethyl substituent shows peculiar behaviour in S l processes647,649. Reaction of a,a,a-trifIuoro-0-iodotoluene (231) with the enolate of 3,3-dimethylbutan-2-one (232) in liquid ammonia under standard photosensitization conditions yields only a minor amount (8%) of the expected substitution product (233), and mainly (43%) a more complex molecule (234) deriving from it (equation 177). Compound 233 is deprotonated... 

The photostimulated reaction of 2-naphthoxide ions (239) with ortho-diiodobenzene (240) in liquid ammonia in the presence of an excess of potassium terf-butoxide gives the substitution product 241 (20%), the cyclized product 242 (16%) and a small amount of Phi (equation 180)663,664. The substitution product 241 is formed via the usual S l reaction. In the solution, 241 is deprotonated and it is proposed that it receives another electron to give... 

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