Sodium acetylide preparation

The sodium acetylide solution thus prepared may be used for a variety of organic syntheses by the addition of alkyl halides, sulfates, sulfonates, ketones, aldehydes, and esters. Where a fine suspension of the dry acetylide is desired in an inert solvent such as ether or a hydrocarbon, the solvent is added to the ammonia solution and the mixture is stirred whde the ammonia is evaporated. Extra solvent must be used to replace that entrained by the ammonia, the last traces of which are removed by a period of refluxing. Such a suspension gives better yields of, for example, propiolic acid (by the reaction with carbon dioxide) than sodium acetylide prepared in any other way. 

Sodium acetylide (prepared from sodium amide) is useful for the condensations with primary alkyl halides. However, secondary, tertiary, and primary halides branched at the second carbon atom are dehydrohalogenated to olefins by the reagent. Iodides react at a faster rate than bromides and the latter faster than chlorides. Chlorides are rarely used. The bromides are more common for preparative reactions. Sodium acetylide can also react with carbonyl compounds to yield acetylenic carbinols. 

To a flask containing a mixture of 5.1 moles of sodium acetylide, prepared during a period of 3 hr from 117 gm of sodium and acetylene in 3 liters of liquid ammonia at -50°C, is added dropwise 5.1 moles (500 gm) of cyclohexanone. The mixture is stirred overnight while a slow stream of dry acetylene is passed through the solution. The ammonia is then evaporated, the residue acidified with 200 gm of tartaric acid in 500 ml of water, and the mixture extracted with ether. The ether layer is dried and evaporated. The residue is fractionated to yield 518 gm (82%) of 1-ethynyl-l-cyclohexanol, bp 74 -77°C (15 mm), 1.4823 and mp 31°-32 C. 

Some unreaeted sodium may be left 011 the walls of the flask in this method and this may partly reduee soino produet, siieh as an alkylaeetylene, derived from the sodium acetylide. The preparation of sodamide is not attended by mueh splashing and little (if any) unreaeted sodium remains on the walls of the flask. Although more manipulation and a somewhat longer time is required for the sodamide method, the latter is generally preferred as it is more adaptable and somewhat less troublesome. 

Ccasionally the reaction mixture does not become completely black nor free from suspended solid here the acetylide is in an insoluble (or sparingly soluble) form, but it gives satisfactory results in the preparation of hex-l-yne. The saturated solution of the soluble form of mono-sodium acetylide in liquid ammonia at — 34° is about i- M. 

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... 

The properties of organometallic compounds are much different from those of the other classes we have studied to this point Most important many organometallic com pounds are powerful sources of nucleophilic carbon something that makes them espe cially valuable to the synthetic organic chemist For example the preparation of alkynes by the reaction of sodium acetylide with alkyl halides (Section 9 6) depends on the presence of a negatively charged nucleophilic carbon m acetylide ion... 

Alkynes of the type RC=CH may be prepared by nucleophilic substitution reactions in which one of the starting materials is sodium acetylide (Na C=CH). 

Reactions in liquid ammonia (cf. Chapter 3, Section III) require a certain amount of care, since the solvent is low boiling (—33 ) and its fumes are noxious. Nevertheless, with reasonable caution, the preparation of an ammonia solution of sodium acetylide can be carried out as described. The reagent so prepared can then be directly used for displacements on alkyl halides or for additions to suitable carbonyl compounds. Examples of both reactions are given. 

The problems of handling liquid ammonia are alleviated in this modification of the sodium acetylide generation procedure. Finely divided sodium is prepared in boiling toluene, the toluene is replaced by THF, and a direct reaction between sodium and acetylene is carried out. The resulting sodium acetylide is employed in ethynylation reactions as before. 

The most convenient method for the preparation of sodium acetylide appears to be by reaction of acetylene with sodium methylsulfinyl carbanion (dimsylsodium). The anion is readily generated by treatment of DMSO with sodium hydride, and the direct introduction of acetylene leads to the reagent. As above, the acetylide may then be employed in the ethynylation reaction. 

Methylsulfinyl carbanion (dimsyl ion) is prepared from 0.10 mole of sodium hydride in 50 ml of dimethyl sulfoxide under a nitrogen atmosphere as described in Chapter 10, Section III. The solution is diluted by the addition of 50 ml of dry THF and a small amount (1-10 mg) of triphenylmethane is added to act as an indicator. (The red color produced by triphenylmethyl carbanion is discharged when the dimsylsodium is consumed.) Acetylene (purified as described in Chapter 14, Section I) is introduced into the system with stirring through a gas inlet tube until the formation of sodium acetylide is complete, as indicated by disappearance of the red color. The gas inlet tube is replaced by a dropping funnel and a solution of 0.10 mole of the substrate in 20 ml of dry THF is added with stirring at room temperature over a period of about 1 hour. In the case of ethynylation of carbonyl compounds (given below), the solution is then cautiously treated with 6 g (0.11 mole) of ammonium chloride. The reaction mixture is then diluted with 500 ml of water, and the aqueous solution is extracted three times with 150-ml portions of ether. The ether solution is dried (sodium sulfate), the ether is removed (rotary evaporator), and the residue is fractionally distilled under reduced pressure to yield the ethynyl alcohol. 

A group of arylalkylketones containing a basic substituent in the side chain shows CNS activities. Roletamide (190) is a hypnotic agent. It is prepared from 3,4,5-trimethoxybenzaldehyde (187) by addition of sodium acetylide (to give 188), followed by Jones oxidation of ethynylarylketone 189. Michael addition... 

Preparation of 4-pentyn-l-ol from 3-bromo-1-propanol and sodium acetylide ... 

Besides the early preparation by Gilman173 of alkynyllead compounds using sodium acetylides and triorganolead halides, and the following modification of the method174 ... 

In one experiment the checkers used 3-butyn-l-ol available from Aldrich Chemical Company, Inc., and found that it was of satisfactory purity. In other experiments, both the submitters and the checkers prepared the hydroxy compound from sodium acetylide and ethylene oxide in liquid ammonia according to the procedure described by Schulte and Reiss3 and further attempted to maximize the yield by varying the ratio of sodium ethylene oxide liquid ammonia used ip the reaction. Unfortunately, the checkers failed to obtain consistent results in repeated experiments and consequently could not define the optimum conditions for the reaction. Thus, the yield of 3-butyn-l-ol varied from 15 to 45% and 15 to 31% on the basis of sodium and ethylene oxide, respectively. Unknown and apparently subtle experimental factors affect the yield significantly. 

The present method developed by the submitters is the only practical process for preparation of l-cyano-6-methoxy-3,4-dihydronaphthalene. Birch and Robinson have reported that 6-methoxy-l-tetralone did not react with hydrogen cyanide or sodium acetylide. 

Diacetylenes having an internal and a terminal triple bond can be reduced selectively at the internal triple bond if they are first converted to sodium acetylides at the terminal bond by sodamide prepared in situ from sodium in... 

Sodium acetylides are the most common reagents, but lithium, magnesium and other metallic acetylides have also been used. A particularly convenient reagent is lithium acetylide-ethylene diamine complex. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. 1,4-Diols can be prepared by treatment of aldehyde with dimetalloacetylenes. 

In the preparation of 1-pentyne and 1-hexyne (exp. 10) complete conversion of the alkyl bromides is effected by using an excess of sodium acetylide. A reasoning based on economics prompts the use of an excess of the alkyl halide if alkali vinylacetylide or alkali diacetylide (generated from alkali amide and dichlorobutene or dichlorobutyne, respectively) are to be alkylated. If slightly mare than the stoichiometiical amount of alkyl bromide is used, no serious separation problems will be encountered during the final distillation. A relatively small amount of DMSO is added to enhance the solubility of the alkyl bromides, thereby facilitating the alkylation reaction. 

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