Sodium. Amide

Sodium amide may be prepared readily from sodium and ammonia in either of two ways by the reaction between liquid ammonia and sodium dissolved in it or by the reaction 

The apparatus for the preparation of sodium amide is shown in Fig. 14. It consists essentially of an iron can or crucible J in which is placed a nickel dish or crucible. 

Reaction vessels of nickel seem to be the most generally useful for the conversion of metal to amide. Vessels of glass and porcelain are rapidly attacked by the amide. Most metals are similarly attacked to a greater or lesser degree. Iron vessels are apt to introduce cyanide.1 3 The can is so arranged that it may be heated and a stream of pure ammonia may be passed into it. 

As soon as the metal melts, the inlet tube, through which the ammonia enters, is pushed beneath the surface of the sodium so that the gas may bubble up through the liquid. With this arrangement, the formation of sodium amide is much more rapid than when the ammonia gas is simply passed over the surface of the sodium.3 The flow of gas 

Gaseous NH3 reacts readily with molten Na at 300 °C and forms NaNH2 [49] by the following reaction  

Furthermore, NaNH2 has been synthesized by ball milling NaH under an NH3 atmosphere at room temperature [50] in the following reaction  

NaNH2 contains 5.1 mass% hydrogen. The crystal structure is orthorhombic (Fddd) [72, 73]. On heating, unlike UNH2, molten NaNH2 does not decompose into the imide and ammonia or nitride and ammonia, but seems to decompose into N2, H2 and Na between 400 and 500 °C through some intermediate reactions. 

Submitted bt K. W. Gbeensc.ee and A. L. Henne Checked bt W. Conabd FEBNEUUst 

In the last few years sodium amide has become increasingly important as a reagent in organic syntheses. Its 

The direct action of pure gaseous ammonia upon pure sodium produces sodium amide of high purity. However, for most uses the material prepared by catalytic reaction of sodium with liquid ammonia at its normal boiling point is preferable because (1) it is finely divided, (2) it is always free of sodium hydride and unconverted sodium, and (3) it can be freed of ammonia, if needed, or left in situ when used further in liquid ammonia. It is well known that the reaction of alkali metals with liquid ammonia is catalyzed by many metals and metal oxides. When the catalytic metal is produced in finely divided form directly in the solution by the reducing action of sodium, the catalytic activity of the metal is greatly enhanced. This method of preparation has attained widespread use. The procedure outlined below is very convenient and requires little special equipment. 

Apparatus. The apparatus consists of a three-necked flask fitted with a mercury-sealed stirrer and a reflux con- 

Unless ventilation is very good, some provision should be made for disposal of the large volumes of hydrogen evolved. Its evolution is observed in a bubbler filled with mineral oil or concentrated aqueous ammonia water is not a suitable liquid because it would be sucked back into other parts of the apparatus. 

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This reaction also occurs slowly when sodium is dissolved in liquid ammonia initially a deep blue solution is formed which then decomposes giving hydrogen and sodium amide. 

The conversion into sodium amide (1 mol) was carried out in a similar way. 

In contrast to the reaction with lithium amide, the sodium amide suspension immediately settles out after stopping the stirring and the supernatant ammonia has a grey or black colour, due to colloidal iron. In some cases it took a long time before all of the sodium had been converted (note 4). A further 0.1 g of iron(III) nitrate was then added to accelerate the reaction and some liquid ammonia was introduced to compensate for the losses due to evaporation. 

A suspension of 0.35 mol of sodium amide in 400 ml of liquid ammonia was prepared in the usual way (e./. Chapter II, Exp. 11) (note 1). To this suspension was added with swirling 0.30 mol of 1-methylthio-l-propyne, in portions of about 10 g, waiting about 10 s after the addition of each portion. Swirling was continued for 1.5 min after the addition of the last portion. Immediately thereafter the... 

A suspension of 0.40 mol of sodium amide in 300 ml of liquid ammonia was prepared as described in Chapter II, Exp. 11. To the suspension was added with swirling a mixture of 0.25 mol of CHgCeC-S-Ph (see Chapter IV, Exp. 14) and 40 ml of THE in about 2 min (note 1). Swirling was continued after the addition. Three minutes later (note 1) the stopper with glass tube was placed on the flask. The brown solution was forced through the glass tube and the plastic tube, connected to it under 400 g of finely crushed ice, which was contained in a 3-1 conical flask (see Chapter I, Fig. 3, and accompanying description of this operation). The flask was placed for... 

Sodium amide in liquid ammonia has been shown to give good results in many 1 40... 

Cumulenic ethers with the 4-positions blocked by alkyl groups can be obtained from bis-ethers, R0-CH2C=C-C(R )(r2)0R, and sodium amide in liquid NHj, applying the... 

Apparatus 3-1 round-bottomed, three-necked flask, provided with a mechanical stirrer- During the addition of the sodium amide suspension the other necks were open. 

Wofcs J. Some experimental skill is required. The sodium amide has to be suspended as homogeneously as possible prior to pouring it into the reaction flask this can be done by vigorous manual swirling, just before the addition. 

A suspension of sodium amide in 500 ml of anhydrous liquid artmonia was prepared from 18 g of sodium (see Chapter II, Exp. 11). To the suspension was added in 10 min with swirling a mixture of 0.30 mol of 1-chloro-l-ethynylcyclohexane (see VIII-2, Exp. 27) and 50 ml of diethyl ether. The reaction was very vigorous and a thick suspension was formed. The greater part of the ammonia was evaporated by placing the flask in a water bath at 50°C. After addition of 500 ml of ice-water the product was extracted three times with diethyl ether. The ethereal extracts were dried over anhydrous KjCOj and subsequently concentrated in a water-pum vacuum. Distillation of the residue afforded the amine, b.p. 54°C/15 mmHg, n 1.4345, in 87% yield. 

Alkynyl anions are more stable = 22) than the more saturated alkyl or alkenyl anions (p/Tj = 40-45). They may be obtained directly from terminal acetylenes by treatment with strong base, e.g. sodium amide (pA, of NH 35). Frequently magnesium acetylides are made in proton-metal exchange reactions with more reactive Grignard reagents. Copper and mercury acetylides are formed directly from the corresponding metal acetates and acetylenes under neutral conditions (G.E. Coates, 1977 R.P. Houghton, 1979). 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

Terminal alkynes are only reduced in the presence of proton donors, e.g. ammonium sulfate, because the acetylide anion does not take up further electrons. If, however, an internal C—C triple bond is to be hydrogenated without any reduction of terminal, it is advisable to add sodium amide to the alkyne solution Hrst. On catalytic hydrogenation the less hindered triple bonds are reduced first (N.A. Dobson, 1955, 1961). 

The terminal diyne 320 is prepared by coupling of the zinc acetylide 318 with /rfln.s-l-iodo-2-chloroethylenc (319), followed by elimination of HCI with sodium amide[231]. Similarly, terminal di- and triynes are prepared by using cw-l,2-dichloroethylene[232]. The 1-alkenyl or l-aryl-2-(perefluoroalkyl) acetylene 321 is prepared by the reaction of a zinc acetylide with halides[233]. 

The classical conditions for the Madelung indole synthesis are illustrated by the Organic Syntheses preparation of 2-methylindole which involves heating o-methylacetanilide with sodium amide at 250 C[1]. 

This reaction, thoroughly studied for 2-aminopyridine (14, 15), has received less attention in the case of the thiazole nucleus. 2-Amino-4-methylthiazole is formed when 4-methylthiazole is heated with sodium amide for 15 hr at 150°C (16). This reaction was used to identify 2-amino-4-butylthiazok (17). 

Similarly, coupling 2-aminothiazole with 2-dimethylaminoethylchloride in the presence of sodium amide yields 2-(2-dimethyla.minoethylamino)-thiazole (42) (186, 187). 

With the exception of the nuclear amination of 4-methylthiazole by sodium amide (341, 346) the main reactions of nucleophiles with thiazole and its simple alkyl or aryl derivatives involve the abstraction of a ring or substituent proton by a strongly basic nucleophile followed by the addition of an electrophile to the intermediate. Nucleophilic substitution of halogens is discussed in Chapter V. 

Water can also be a Brpnsted acid donating a proton to a base Sodium amide (NaNH2) for example is a source of the strongly basic amide ion which reacts with water to give ammonia... 

Solutions of sodium acetylide (HC=CNa) may be prepared by adding sodium amide (NaNH2) to acetylene m liquid ammonia as the solvent Terminal alkynes react similarly to give species of the type RC=CNa... 

Alkylation of acetylene involves a sequence of two separate operations In the first one acetylene is converted to its conjugate base by treatment with sodium amide... 

Geminal dihalide Sodium amide Alkyne Ammonia... 

Alkyne Sodium Ammonia Trans alkene Sodium amide ... 

Acetylene and terminal alkynes are more acidic than other hydrocarbons They have s of approximately 26 compared with about 45 for alkenes and about 60 for alkanes Sodium amide is a strong enough base to remove a proton from acetylene or a terminal alkyne but sodium hydroxide is not... 

The acidity of acetylene and terminal alkynes permits them to be converted to their conjugate bases on treatment with sodium amide These anions are good nucleophiles and react with methyl and primary alkyl halides to form carbon-carbon bonds Secondary and tertiary alkyl halides cannot be used because they yield only elimination products under these conditions... 

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