Sodium acetylide alkyl halides

Next an alkyl halide (the alkylating agent) is added to the solution of sodium acetylide Acetylide ion acts as a nucleophile displacing halide from carbon and forming a new carbon-carbon bond Substitution occurs by an 8 2 mechanism... 

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... 

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. 

What is an immediate precursor of a terminal alkyne " Perhaps sodium acetylide and an alkyl halide. 

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. 

Dialkylacetylenes. A convenient method for the prepn of dialkylacetylenes, RC CR, is described in which the process involves interaction of sodium acetylide, sodamide alkyl halides in iq ammonia. Intermediate products are not isolated, thereby saving substantial time as compared with older methods. The following pure compds were prepd ... 

Alkali metal acetylides obtained from acetylenes and sodium in liquid ammonia1 react with tellurium powder to yield sodium ethynetellurolates that are easily alkylated with alkyl halides. 

We have already encountered one type of organometallic compound with a negative charge on carbon sodium acetylides, covered in Section 9-7. Terminal alkynes are weakly acidic, and they are converted to sodium acetylides by treatment with an unusually strong base, sodium amide. These sodium acetylides are useful nucleophiles, reacting with alkyl halides and carbonyl compounds to form new carbon-carbon bonds. 

This method finds commercial application in the production of acetaldehyde from acetylene. Mercuric salts in the presence of dilute sulfuric acid act as the catalyst. The reaction has been extended to higher alkylacetylenes, which are obtained in about 60% yield from sodium acetylide and alkyl halides. These compounds are readily hydrated in aqueous solutions of acetone, methanol, or acetic acid to give 80-90% yields of the corresponding methyl ketones, fot example, methyl butyl, methyl amyl, and methyl hexyl ketones. Hydration has been accomplished by passing the acetylenic hydrocarbon and steam over a phosphoric acid catalyst at 150-204° and atmospheric pressure. ... 

The acetylide ion is a strongly basic and nucleophilic species which can induce nucleophilic substitution at positive carbon centres. Acetylene is readily converted by sodium amide in liquid ammonia to sodium acetylide. In the past alkylations were predominantly carried out in liquid ammonia. The alkylation of alkylacetylenes and arylacetylenes is carried out in similar fashion to that of acetylene. Nucleophilic substitution reactions of the alkali metal acetylides are limited to primary halides which are not branched in the -position. Primary halides branched in the P-position as well as secondary and tertiary halides undergo elimination to olefins by the NaNH2. The rate of reaction with halides is in the order I > Br > Cl, but bromides are generally preferred. In the case of a,o)-chloroiodoalkanes and a,to-bromoiodoalkanes. 

Lithium acetylide is best prepared from acetylene and LiNH in liquid ammonia. Lithium acetylides are more soluble in liquid ammonia than sodium acetylides and therefore give higher yields (50-80%) on reaction with higher halides. trans-2-Alken-4-ynols have been generally obtained on alkylation of sodium acetylides with... 

The reaction between sodium acetylide and alkyl halides in liquid ammonia is the most general method of preparing substituted acetylenes. It has very often been used to prepare labelled alkynes . Appropriately labelled alkyl halides have to be prepared first (a review of the preparation of the most common ones has already been given ), but more and more are now commercially available. The yield of the condensation in liquid ammonia is about 75% and, under experimental conditions, no isotopic exchange has been found the isotopic purity of the final alkynes is the same as that of the starting alkyl halides. 

Reaction of sodium acetylides wkh primary alkyl halides. Discussed in Sec. 8.12. 

Reaction of sodium acetylides with alkyl halides permits conversion of smaller alkynes into larger ones. Practically, the reaction is limited to the use of primary halides because of the great tendency for secondary and tertiary halides to undergo a side reaction, elimination this point will be discussed further (Sec. 8.12) after we have learned something about the nature of acetylides. 

Reaction of sodium acetylides with alkyl halides. Substitution vs, elimination... 

Since sodium acetylide is the salt of the extremely weak acid, acetylene, the acetylide ion is an extremely strong base, stronger in fact than hydroxide ion. In our discussion of the synthesis of alkenes from alkyl halides (Sec. 5.13), we saw that the basic hydroxide ion causes elimination by abstracting a hydrogen ion. It is not surprising that the even more basic acetylide ion can also cause elimination. 

Alkylation of sodium acetylides by alkyl halides or sulfates also occurs smoothly and under mild conditions when dimethyl sulfoxide is used as solvent 487 and, as mentioned above, sodium acetylides can be prepared simply in this medium. 

Sodium acetylide can react with alkyl halides in a substitution reaction to produce higher alkynes. The reaction involves substitution of acetylide ion for halide ion as shown ... 

Sodium acetylides react with primary alkyl halides in a substitution reaction to give alkynes of carbon skeleton greater than two. Hence, if methyl iodide is added to sodium acetylide, propyne results ... 

The alkyl azide is generated in situ from the corresponding alkyl halides and sodium azide, whereupon it is captured by copper(I) acetylide forming the desired triazole 45. The reaction is performed under the action of MW irradiation for 10 min at 125 °C. Although most compounds readily tolerated this temperature, occasionally it resulted in reduced yields. To circumvent these problems these reaction mixtures were irradiated for 15 min at 75 °C. The reaction was performed in a 1 1 mixture of t-BuOH and water and the Cu(I) catalyst was prepared in situ by... 

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