Deprotonations, sodium hydride

Oxygen Acids (Alcohol Deprotonation). Sodium hydride may be used as a base in the Williamson ether s)uithesis in neat benzyl chloride, in DMSO, or in THE (eq 2)f Phenols may also be deprotonated and alkylated in THE. ... 

A AlI lation. 1-Substitution is favored when the indole ring is deprotonated and the reaction medium promotes the nucleophilicity of the resulting indole anion. Conditions which typically result in A/-alkylation are generation of the sodium salt by sodium amide in Hquid ammonia, use of sodium hydride or a similar strong base in /V, /V- dim ethyl form am i de or dimethyl sulfoxide, or the use of phase-transfer conditions. 

Both NaH and KH are used to deprotonate alcohols. KH is more reactive than NaH. Compare atomic charges and electrostatic potential maps of potassium hydride and sodium hydride. For which is the hydrogen more negatively charged Which should be the better source of hydride ... 

One method to transform imidazolium salts (00AGE3773) into carbene ligands, imidazol-2-ylidenes, is by deprotonation with sodium hydride or other suitable hydride in a mixture of THE and liquid ammonia (73JCS(D)514, 96CEJ1627, 98IC6412). 

Because carbonyl compounds are only weakly acidic, a strong base is needed for enolate ion formation. If an alkoxide such as sodium ethoxide is used as base, deprotonation takes place only to the extent of about 0. l% because acetone is a weaker acid than ethanol (pKa - 16). If, however, a more powerful base such as sodium hydride (NaH) or lithium diisopropylamide ILiNO -CjHy ] is used, a carbonyl compound can be completely converted into its enolate ion. Lithium diisopropylamide (LDA), which is easily prepared by reaction of the strong base butyllithium with diisopropylamine, is widely used in the laboratory as a base for preparing enolate ions from carbonyl compounds. 

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. 

Secondary amides can be alkylated on nitrogen by using sodium hydride for deprotonation, followed by reaction with an alkyl halide.62... 

On the other hand, deprotonation of cycloadduct 76 with sodium hydride in acetonitrile at 0°C afforded cyclic sulfilimine 78, the so-called 1,2-azathiabenzene derivative, together with a spiro compound 79 (see Equation (21) and Table 11) <1999TL1505>. 

A complementary method was reported 3 years later by Hino, in which a readily enolizable diketopiperazine 48 was directly converted to the epidisulfide by deprotonation with sodium hydride and exposure to sulfur monochloride [38]. As with the Trown method, this method was limited to a specific class of substrates, namely, ones possessing a 1,3-dicarbonyl motif at each of the reactive centers, yet it has also seen subsequent applications in total synthesis [39, 40]. In 1972, Schmidt was able to significantly broaden the scope of the enolate thiolation method by introducing elemental sulfur as the electrophilic agent [41]. In contrast to Hino s method in which formation of a highly reactive, unstable adduct requires readily... 

A somewhat related microwave-promoted 5 -0-allylation of thymidine has been described by the Zerrouki group (Scheme 6.108) [215], While the classical method for the preparation of 5 -0-allylthymidine required various protection steps (four synthetic steps in total), the authors attempted the direct allylation of thymidine under basic conditions. Employing sodium hydride as a base at room temperature in N,N-dimethylformamide resulted in the formation of per-allylated compounds along with the desired monoallylated product (75% yield). The best result was achieved when both the deprotonation with sodium hydride (1.15 equivalents) and the subsequent allylation (1.2 equivalents of allyl bromide) were conducted under... 

When l,2,3,4-tetrakis(4-pyridinyl)cyclobutane is treated with ethyl chloroformate in the presence of ethyldiisopropylamine, radialene 74a is formed and can be isolated as red crystals. Addition of AgBEt to a red solution of 74a results in an immediate color change to deep blue caused by the formation of the dicationic species 75a (equation 5)43. Undoubtedly, the tetrapyridiniocyclobutane 73a is an intermediate in the formation of 74a. By way of contrast, the fourfold deprotonation of the analogous tetrakis(7V-methyl-4-pyridinyl)cyclobutane (73b) did not succeed in the presence of oxygen. Treatment with NaH/EtOH in the presence of oxygen produced the dication 75b, which could be reduced to the [4]radialene only electrochemically44. Deprotonation of 73b with sodium hydride... 

Sodium hydride in THF can be used with advantage to deprotonate nitro derivatives of carbohydrates in the presence of Bu Me2SiCl (182, 183). In these cases, the yields of respective SENAs are 60% to 80%. 

Products of the deprotonation of [nido-2,3-(SiMe3)2-2,3-C2B4H6] with sodium hydride or -butyllithium have been characterized in solution and in the solid state.9,10... 

The synthesis of the basic skeleton of 1-benzylisoquinoline alkaloids has been reported by Uff et al. 15) starting from isoquinoline and benzyl chloride (Scheme 5). The preparation of Reissert compound iV-benzyl-l-cyano-l,2-di-hydroisoquinoline (4) was performed in a dichloromethane-water two-phase system with potassium cyanide and benzoyl chloride in about 64-69% yield. The deprotonation of 4 with sodium hydride in dimethylformamide solution, the subsequent alkylation with benzyl chloride, and the final alkaline hydrolysis could be performed as a one-pot reaction sequence to supply 1-benzylisoquinoline (25) in an overall yield of 75-84%. 

The synthesis of anastrozole (Scheme 3.3) began with an 8 2 displacement of commercially available 3,5-fc (bromomethyl)toluene (19) using potassium nitrile and a phase-transfer catalyst, tetrabutylammonium bromide (Edwards and Large, 1990). The resulting fcw-nitrile 20 in DMF was then deprotonated with sodium hydride in the presence of excess methyl iodide to give the fc -dimethylated product 21. Subsequently, a Wohl-Ziegler reaction on 21 was carried out using A-bromosuccinamide (NBS), and a catalytic amount of benzoyl peroxide (BPO) as the radical initiator. Finally, an Sn2 displacement of benzyl bromide 22 with sodium triazole in DMF afforded anastrozole (2) as a white solid. 

In order to access the C-2 position, indirect methods of reaction are used, and a common procedure is to A-sulfonate indole with sodium hydride and benzenesulfonyl chloride and then to treat the derived sulfonate with butyllithium. C-2 deprotonation and lithiation occur (facilitated by chelation to the sulfonyl group) and the intermediate, without isolation, can then be reacted with a wide range of electrophiles at this site. Finally, the sulfonyl group can be hydrolysed off in a separate step to form the desired product (Scheme 7.10). 

N-Methylation of 139 with iodomethane in nitromethane afforded 2,3,4,4,6-pentamethyl-5,6-dihydro-4/7-oxazi-nium iodide 140. Deprotonation of 140 with sodium hydride resulted in formation of the cyclic ketene-A, 0-acetal derivative tetrahydro-l,3-oxazine 141 (Scheme 21) <2006JC0262>. 

Ueno and Okawara (184) were the first to explicitly formulate a conjugated thiocarbonyl ylide as an intermediate in the reaction of l,3-dithiolane-2-thione with 4-bromophenacyl bromide. The initially formed thiocarbonyl ylide undergoes deprotonation with sodium hydride to give 2-(4-bromophenyl)-l-oxa-4,6,9-trithias-piro[4.4]non-2-ene. 1,3-Diacylated thiocarbonyl ylides of type 149 (Scheme 5.45) have also been proposed as intermediates in the reaction of 1,3-diphenylpropane-1,3-dione with thionyl chloride. This reaction leads to 2,2,4-tribenzoyl-5-phenyl-... 

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