Alkynides alkyl halides

The alkyl halide used with the alkynide anion must be methyl or primary and also unbranched at its second (beta) carbon. 

The alkynide anion is a Lewis base and reacts with the alkyl halide (as an electron pair acceptor, a Lewis acid). 

Electrostatic potential maps illustrate the complementary nucleophilic and electrophilic character of the alkynide anion and the alkyl halide. 

Metal acetylides or alkynides react with primary alkyl halides or tosylates to prepare alkynes (see Sections 5.5.2 and 5.5.3). 

They react with alkyl halides to give internal alkynes (see Section 5.5.2) via nucleophilic substitution reactions. This type of reaction also is known as alkylation. Any terminal alkyne can be converted to acetylide and alkynide, and then alkylated by the reaction with alkyl halide to produce an internal alkyne. In these reactions, the triple bonds are available for electrophilic additions to a number of other functional groups. 

We have already learnt that alkyl halides react with alcohols and metal hydroxide (NaOH or KOH) to give ethers and alcohols, respectively. Depending on the alkyl halides and the reaction conditions, both S l and Sn2 reactions can occur. Alkyl halides undergo a variety of transformation through Sn2 reactions with a wide range of nucleophiles (alkoxides, cyanides, acetylides, alkynides, amides and carboxylates) to produce other functional groups. 

Preparation of alkynes The reaction of primary alkyl halides and metal acetylides or alkynides (R C=CNa or R C=CMgX) yields alkynes. The reaction is limited to 1° alkyl halides. Higher alkyl halides tend to react via elimination. 

Silver nitrate test The compound to be tested is treated with a few drops of 1% alcoholic silver nitrate. A white precipitate indicates a positive reaction. This could be due to either silver chloride (reaction with a reactive alkyl halide), silver alkynide (reaction with a terminal alkyne), or the silver salt of a carboxylic acid (reaction with a carboxylic acid). 

Once the alkynide is formed, it can be treated with an alkyl halide to form more complex alkynes. This reaction is called an alkylation and is an example of nucleophilic substitution. 

This reaction works best with primary alkyl halides. When secondary or tertiary alkyl halides are used, the alkynide reacts like a base and this results in elimination of hydrogen halide from the alkyl halide to produce an alkene ... 

The insertion tendency decreases in the order r-BuLi > 5-BuLi > n-BuLi > PhLi > MeLi. These insertions can be carried out by using lithium alkanides, alkenides, alkynides, and aromatic or heterocyclic lithium compounds. The lithiation should not be carried out by using alkyl halides, because the lithium tellnrolates that are formed in the reaction may react with the alkyl halide reagent to produce organyl alkyl tellurides. ... 

Alkynide anions are useful nucleophiles for carbon-carbon bond forming reactions with primary alkyl halides or other primary substrates. 

The following are general and specific examples of carbon—carbon bond formation by alkylation of an alkynide anion with a primary alkyl halide. 

The alkynide anion acts as a nucleophile and displaces the halide ion from the primary alkyl halide. We now recognize this as an 5 2 reaction (Section 6.5). 

Primary alkyl halides should be used in the alkylation of alkynide anions, so as to avoid competition by elimination. 

One very important aspect of retrosynthetic analysis is being able to identify those atoms in a target molecule that could have had complementary (opposite) charges in synthetic precursors. Consider, for example, the synthesis of 1-cyclohexyl-1-butyne. On the basis of reactions learned in this chapter, you might envision an alkynide anion and an alkyl halide as precursors having complementary polarities that when allowed to react together would lead to this molecule ... 

The alkynide anion and alkyl halide have complementary polarities. 

This reaction has powerful synthetic utility, because the resulting alkynide ion can function as a nucleophile when treated with an alkyl halide ... 

Count the carbon atoms in the starting material and in the desired product. There are seven carbon atoms in the starting material, and there are nine carbon atoms in the product. Therefore two carbon atoms must be installed. We have only learned one reaction capable of installing two carbon atoms on an existing carbon skeleton. This process requires the use of an alkynide ion and an alkyl halide ... 

Alternatively, this reaction can be viewed from the perspective of the alkyl halide. That is, the alkyl halide is the starting material, and an alkynide ion is used to achieve the installation of a triple bond onto an existing carbon skeleton ... 

These syntheses can be accomplished by treating the sodium alkynide with a primary alkyl halide ... 

Figure 7.8 The reaction of ethynide (acetylide) anion and chloromethane. Electrostatic potential maps illustrate the complementary nucleophilic and electrophilic character of the alkynide anion and the alkyl halide. The dipole moment of chloromethane is shown by the red arrow.

Alkynide ions react with carbonyl groups in much the same way as Grignard reagents do. We recall that these ions are effective nucleophiles that will displace a hahde ion ftom an alkyl halide to give an alkylated alkyne. The alkynides are prepared in an acid-base reaction with acetylene or a terminal alkyne using sodium amide in ammonia. If a carbonyl compound is then added to the reagent, an alcohol forms after acid work-up. If the alkynide is derived ftom acetylene, an acetylenic alcohol forms. 

In some respects, the alkylation of enolate anions resembles nucleophilic substitution. We recall that many nucleophiles displace leaving groups from primary alkyl halides by an Sj 2 mechanism (Section 9.3). A similar reaction occurs with secondary alkyl halides, but competing elimination reactions also occur. Primary alkyl halides react with carbanions, such as the alkynide ion, by an Sj 2 mechanism. (Secondary alkyl halides react not only in displacement reactions but also in elimination reactions because the alkynide ion is a strong base.)... 

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