Sodium amide, as base

Liquid ammonia (b.p. -33°C) is a solvent which is not encountered frequendy, but which does have several important general uses, in particular dissolving metal reductions ("Birch" type reductions) and most reactions involving lithium amide or sodium amide as bases. Ammonia gas from a cylinder is condensed directly into the flask (Fig. 14.5). 

Initial studies of solvent effects, on the reactions of triarylarsonium benzoylylides with p-nitrobenzaldehyde in N, A-dimethylformamide, dimethyl sulphoxide or methanol, indicated little solvent effect in these cases" ", but later studies of the more finely balanced reactions of semi-stabilized ylides have provided examples of strong influences due to the effect of different base and solvent when the ylide is generated in the presence of a carbonyl compound ". Thus, when benzyltriphenylarsonium bromide or p-chloroben-zyltriphenylarsonium bromide were treated with sodium hydride in benzene in the presence of a variety of p-substituted benzaldehydes the products were alkenes, but if sodium ethoxide in ethanol was used the isolated products were epoxides ". Likewise, when triphenylarsonium benzylylide was generated by phenyllithium in the presence of either benzaldehyde or acetaldehyde, the preponderant product was the epoxide whereas use of sodium amide as base provided mostly the alkene . Similar results were obtained when an allyltriphenylarsonium salt was deprotonated using different hexamethyldisilaz-... 

The reagent is selective toward ketosteroids. 3-Ketosteroids and A -3-keto-steroids react readily, but keto groups at Ce, C7, and C, are unreactive to the reagent. Japanese workers have used sodium amide as base and tetrahydrofurane as solvent. ... 

Although further study will be necessary before we can evaluate the relative importance of all the chemical events on the observed extractabil-ities, the cleavage of covalent cross-links probably is not a major chemical event under these base conditions. In contrast, as Stock and Mallya (21) noted, the cleavage of covalent cross-links may be important when PSOC 1197 is subjected to base-promoted alkylation using sodium amide as base. 

Amide ion. See also Sodium amide as base, 346-349, 359, 556, 848 in nucleophiUc aromatic substitution reactions, 927—931... 

Clemastine Clemastine, 2-[2-[l-(4-chlorophenyl)-l-phenylethoxy]ethyl]-l-methylpyrroli-dine (16.1.4), is synthesized by reacting l-(4-chlorophenyl)-l-phenylethanol (16.1.3) with 2-(2-chlorethyl)-2-methylpyrrolidine using sodium amide as a base. The starting l-(4-chlorophenyl)-l-phenylethanol (16.1.3) is synthesized either by reacting 4-chloroben-zophenone with methylmagnesium chloride, or by reacting 4-chloroacetophenone with phenylmagnesium bromide [6-8]. 

Prior to the recent paper by Buchwald, an intermolecular version of the arylation of carbamates was published by Hartwig et al. (Eq. (22)) [163]. His group showed that reactions catalyzed by a combination of Pd(OAc)2 and P(tBu)3 formed N-aryl carbamates from aryl bromides or chlorides and tert-butyl carbamate, but that this system was inactive for reactions of amides or sulfonamides. Again, the reaction conditions were not as mild as those used for animation, but they were similar to those employed in the reactions with Xantphos. For the intermolecular reactions, the use of sodium phenoxide as base was crucial. 

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... 

As can be seen from Table 1 sodium tert-butoxide gives similar results compared to lithium amides as base (entries 1 and 2). Both are superior to lithium tcrt-butoxide (entries 3 and 4). Since NaOtBu is easier to handle it seems to be the base of choice for this reaction. With tri-o-tolylphosphine as ligand the procedure is limited to secondary amines. Nevertheless, some application of this new method - mainly from industrial... 

Two basic synthetic routes have been reported for the preparation of propiomazine hydrochloride. Farbenfabriken Bayer prepared propiomazine by reacting 2-dimethyland.no-propyl chloride with 2-propionylphenothiazine in the presence of sodium amide as the condensing agent, and subsequently converting the base form to the hydrochloride (See Figure 6). 

Piers et al used sodium bis(trimethylsilyl)amide as base for the decomposition of a hydrazone (3) containing a nonenolizable keto group. 

Compared to that of the Ruzicka protocol, the Claisen-Geuther ester condensation in this synthesis was optimized from 17% to 64% by replacement of sodium ethoxide with sodium or sodium amide. In addition, the cyclization to form the piperidinyl ring is carried out in a two-phase solvent system (H2O and ether) using sodium carbonate as base. ... 

As we shall soon see, sodium amide (NaNH2) is useful, especially when a reaction requires a very strong base. Explain why a solvent such as methanol cannot be used to carry out a reaction in which you might want to use sodium amide as a base. 

The reagent formation is in some cases dramatically improved by sonication. An example using sodium amide as the base constitutes an illustration (Eq. 18). 2 Without sonication, the ylide does not form at all. 

III. 3.A.b), is occurring during the reaction of 2-bromothiophene (317) with potassium and sodium amides as well and therefore may be involved in the formation of both 3-amino- (318) and 3-bromothiophene (319). The latter compound would be expected to be formed, via the sodio derivative 296, if the ECHO mechanism were operative by analogy to the isomerization of 2-bromo-3-lithiothiophene (303) to the more stable 3-bromo-2-lithiothiophene (294). The validity of this hypothesis was established by a series of experiments, the most significant of which showed that many of the polybromothiophenes in Table 6 could be converted to 3-bromothiophene (319) under conditions which also favored its formation from 317 (low NHj concentration as is obtained when the relatively insoluble NaNH2 is used as a base in liquid... 

Reactions.—A-Alkylation of acetanilides has been achieved using a two-phase system of water and benzene with sodium hydroxide as base and triethylbenzylam-monium chloride yields are better than 80%. An efficient two-step process for the A-methylation of unsubstituted amides, lactams, and ureas has been described which involves initial formation of the corresponding methylol, by treatment with formaldehyde, followed by reduction with either triethylsilane and trifluoroacetic acid or with hydrogen over palladium in TFA. A method for the methylthiomethy-lation of both amides and lactanes has appeared. ... 

The usual method of preparing monohalogenocyclopropanes has previously been by reduction of the relatively easily accessible dihalogeno-derivatives. A new one-step production of monohalogenocyclopropanes has been reported which uses dihalogenomethanes and sodium bis(trimethylsilyl)amide as base. Yields of up to 54% were obtained from cycloaddition to simple olefins. The method was highly stereoselective for bromocyclopropanation of cyclo-octene ids trans = 20) but much less so in other cases. 

Which isomer, 2,2-dibromopentane or 3,3-dibromopentane, would give the better yield of 2-pentyne using sodium amide as the base ... 

The bis(2,2,2-triiluoroethyl) dithiocarbamate salt, NaS2CN(CH2CF3)2, is a valuable precursor to a range of complexes that find widespread uses in analytical chemistry (74-82). It can be readily prepared from the amine using sodium amide as the base in the presence of carbon disulfide (Eq. 5) (76, 75), and a synthesis of the lithium salt has also been reported (83, 84). 

Substances like ammonium chloride are acids, and substances like sodium amide are bases, in liquid ammonia. Ammonia solutions of acids and bases neutralize each other just as aqueous solutions do. For example ... 

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