Sodium hydride as base

Many acylation reactions of esters using sodium hydride as base appear auto-catalytic, with considerable potential for runaway, since the active base in solution is an alkoxide and the alcohol is a product of reaction [4], A safe form of sodium hydride (as a solid solution in a halide) for large-scale industrial use has been claimed [3],... 

C-5 substituent either a pyrimidine (98) (when = NR2) or an isothiazole (99) (when R = Ar) are finally obtained. Sodium hydride as base resulted in ring fragmentation to give the open-chain adduct (100). Multistep mechanisms are proposed for these transformations (89BCJ1086>. The behavior of methylthio and dialkylamino salts (5 R = SMe and NRj, respectively) is quite similar and both give with carbon nucleophiles (e.g. Meldrum s acid) the same alkylidene derivative (97) (X , = Meldrum s acid residue) <(85CC696,88JCS(P1)899>. 

Sodium hydride as base with epichlorhydrin was utilized to prepare 29... 

Asymmetric Michael additions. In the presence of sodium hydride as base, the /-butyl ester of 1 undergoes conjugate addition to a,/ -unsaturatcd esters (but not to ketones) with 12-24% asymmetric induction. The reaction was used to prepare optically active <5-lactones. 

The reaction of 3//-pyrrolizines (244) with vinyleneamidinium salts (245) provides a direct route to [2.2.3]cyclazines. [2.2.3]Cyclazine (229) was, in fact, obtained by this method, using sodium hydride as base, but the yield (2.8%) was very low (80JCS(P1)1319). However, a 35% yield of 1-substituted [2.2.3]cyclazines (246) has been obtained from the corresponding 3//-pyrrolizines (244) (81UP30802). 

Condensation of dicyclopropyl ketone with diethyl succinate using sodium hydride as base gave... 

During the benzylation of an alcohol the hydroxy functionalities are turned into alkoxides. Therefore NaH is necessary. Next benzyl bromide is added. For an efficient alkylation using sodium hydride as base dipolar aprotic solvents like DMF or DMSO are necessary.22 During the benzylation a reversible TDS rearrangement between C-la and C-2a of the lactose occurs.23 First deprotonation with NaH leads to C-2a-oxide 44 formation and then to the rearrangement. 

Nalmefene can be synthesized by a Wittig reaction of naltrexone with tri-phenylphosphonium bromide in dimethyl sulphoxide with sodium hydride as base [57],... 

The reaction of keto phosphonates with sodium hydride as base is applicable to the synthrais of a,p-unsaturated carbonyl compounds, even under the conditions of the dOution principle [78]. Thus the keto phosphonate 104 could be transformed by this cyclization reaction into the mixture of the epimers 105 in 28-36% yield. 

A more ingenious route involves the dehydrobromination of ester 1 in a benzene solution containing a catalytic amount of ethanol and using sodium hydride as base. The ethoxide ion, being a stronger base in benzene than in ethanol, deprotonates the substrate and is converted to ethanol. As a result much less ethoxide is available for addition to the triple bond, thus affording the ethyl phenylpropiolate and the ethyl P-ethoxycinnamate in ca. 56% and 27% yield, respectively . 

In the original procedure Wadsworth and Emmons used sodium hydride as base and 1,2-dimethoxyethane as solvent. In a Japanese procedure sodium amide is used as base and tetrahydrofurane as solvent. The reagent reacts with steroids having a keto group at C3, Cn, or Cio and is thus less selective than triethylphosphonoacetate,... 

Fones alkylated a number of N-substituted amides with sodium hydride as base and found it more convenient than sodium. Marvel and Moyer " used this method... 

However, when an ethereal solution of 4-tosyloxycyclohexanone (la) was treated with sodium triphenylmethanide and heated under reflux, no bicyclic ketone was isolated. By using a higher boiling solvent (benzene) with the same base, the bicyclic ketone was obtained in 12% yield. When the reaction was carried out in refluxing dioxane, the yield increased to 57%. The best yield with sodium triphenylmethanide, 64%, was achieved using sodium hydride as base and dioxane as solvent. 

Cyclopentanone annulation via a cyclopropoxide anion has great synthetic applicability. Construction of the D-ring in estrone can be achieved by base-induced intramolecular cyclization of an appropriately substituted cyclopropanol using sodium hydride as base (Table 2, entry 23-24 jjjg j-esyit is well accounted for by assuming intramolecular carbonyl addition of a j3-acyl carbanion. 

The reaction of all-/ra/i5-/ -ionylideneacetaldehyde with the phosphonium salt (79), using sodium hydride as base, gave a mixture of furanones as shown. ... 

For alkylation of malonodinitrile, dimethyl sulfoxide is recommended as solvent and sodium hydride as base, the reaction then occurring faster, under milder conditions, and in better yield than by other procedures. Wbenzyl-malonodinitrile, for instance, is thus obtained in 64-76% yield 412... 

An oxo ester group can be introduced similarly (96% yield) in the 2-position of 1-tetralone 753 under mild conditions, with sodium hydride as base, 2,6-lutidine TV-oxide gives a 91% yield of ethyl 3-(6-methyl-l-oxido-2-pyridyl)-pyruvate 754. . 

Acetylation activates the second alcohol to displacement so that the combination of sodium hydride as base and palladiumfO) catalyst leads to cyclization to the cyclopropane. 

By aldol condensation between the Cio-building block 175 and crocetindialdehyde (536), with sodium hydride as base, capsorubin (413) was synthesized in a yield of 32% (Scheme 42). 

Most of the hydroxylated pulvinic acids from Basidiomycetes were first synthesised (7i, 200, 607, 608, 609) using the classical methods of VoLHARD 687) and Asano (52). For unsymmetrically substituted pulvinic acids such as xerocomic acid (72) the procedure is shown in Scheme 12 202). The use of sodium hydride as base in the second condensation step is recommended ( ) in order to reduce contamination of the dinitrile (99) with symmetrical by-products which arise via retro-aldol processes when sodium ethoxide is used. This route has also been followed for the synthesis of " C-labelled compounds 514). 

Abstract. Crown ethers derived from tartaric acid present a number of interesting features as receptor frameworks and offer a possibility of enhanced metal cation binding due to favorable electrostatic interactions. The synthesis of polycarboxylate crown ethers from tartaric acid is achieved by simple Williamson ether synthesis using thallous ethoxide or sodium hydride as base. Stability constants for the complexation of alkali metal and alkaline earth cations were determined by potentiometric titration. Complexation is dominated by electrostatic interactions but cooperative coordination of the cation by both the crown ether and a carboxylate group is essential to complex stability. Complexes are stable to pH 3 and the ligands can be used as simultaneous proton and metal ion buffers. The low extractibility of the complexes was applied in a membrane transport system which is a formal model of primary active transport. 

This methodology was also applied in the first enantioselective syntheses of (+)-dictyopterene A and C, isolated from Hawaian seaweed belonging to genus Dictyopteris and presenting physiological activities (Scheme 2). The key intermediate, allylic benzoate 7, was prepared in a few steps starting from trimethylsilylacetylene 6, with 85% enantiomeric excess. The Pd-catalyzed reaction of 7 in the presence of a catalytic amount of Pd(dppe)2 and sodium hydride as base led cleanly to cyclopropane 8, which was desul-fonylated, reduced, and oxidized to give a mixture of cis- and trans- (60 40) aldehydes. 

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