Sodium amide reaction

Butylation of ethyl phenylacetate, /-butyl phenylacetate, and ethyl 2-phenylhexanoate has also been accomplished with M-butyl bromide and sodium hydride in refluxing monoglyme in 64%, 66%, and 56% yields, respectively.6 In contrast to the sodium amide reactions above, however, careful fractionation of the crude products was required to obtain pure products. 

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. 

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. 

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). 

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]. 

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). 

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. 

Double dehydrohalogenation of gemmal dihalides (Section 9 7) An E2 elimination reaction of a gemmal dihalide yields an alkenyl halide If a strong enough base IS used sodium amide for example a second elimination step follows the first and the alkenyl halide IS converted to an alkyne... 

When 1 2 dibromodecane was treated with potassium hydroxide m aqueous ethanol it yielded a mixture of three isomenc compounds of molecular formula CioHi9Br Each of these compounds was converted to 1 decyne on reaction with sodium amide m dimethyl sulfoxide Men tify these three compounds... 

Double dehydrohalogenation (Section 9 7) Reaction in which a geminal dihahde or vicinal dihahde on being treated with a very strong base such as sodium amide is converted to an alkyne by loss of two protons and the two halogen substituents... 

Acetaldehyde reacts with phosphoms pentachloride to produce 1,1-dichloroethane [75-34-3] and with hypochlorite and hypoiodite to yield chloroform [67-66-3] and iodoform [75-47-8], respectively. Phosgene [75-44-5] is produced by the reaction of carbon tetrachloride with acetaldehyde in the presence of anhydrous aluminum chloride (75). Chloroform reacts with acetaldehyde in the presence of potassium hydroxide and sodium amide to form l,l,l-trichloro-2-propanol [7789-89-1] (76). 

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. 

Refluxing linoleic acid and a primary or secondary alkyl amine with -toluenesulfonic acid in toluene for 8—18 h also yields the substituted amides (32—34). The reaction of methyl esters with primary or secondary amines to make substituted amides is catalyzed with sodium methoxide. Reactions are rapid at 30°C under anhydrous conditions (35). Acid chlorides can also be used. Ai,A/-dibutyloleamide [5831-80-17 has been prepared from oleoyl chloride and dibutyl amine (36). 

Phosphoms trichloride and pentachloride form sodium chloride and sodium phosphide, respectively, in the presence of sodium. Phosphoms oxychloride, POCl, when heated with sodium, explodes. Carbon disulfide reacts violendy, forming sodium sulfide. Sodium amide (sodamide), NaNH2, is formed by the reaction of ammonia gas with Hquid sodium. SoHd sodium reacts only superficially with Hquid sulfur dioxide but molten sodium and gaseous... 

The ring opening of 3-substituted isoxazoles proceeds differently, and the reaction can take various courses depending on the nature of the substituent. The reaction has been effected by sodium hydroxide and sodium ethoxide in alcoholic or aqueous media and by sodium amide and also n-butyllithium in inert solvents. 

Complete conversion into sodium amide is indicated by cessation of gas evolution and disappearance of the blue color of the solution. This generally requires 20-30 minutes and results in a gray suspension of sodium amide in a dark-gray reaction medium. 

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