Alkynes using acetylide ions

Organic compounds can be metalated at suitably acidic positions by active metals and by strong bases.The reaction has been used to study the acidities of very weak acids (see p. 228). The conversion of terminal alkynes to acetylid ions is one... 

Using retrosynthetic analysis, we recognize that the c/.v-epoxide can be prepared from the c/s-alkene. The m-alkene can be prepared by catalytic hydrogenation of an alkyne. Finally, substituted alkynes can be prepared by nucleophilic substitution reactions using acetylide ion nucleophiles (see Section 10.8). On the basis of this analysis, the synthesis reported in the literature was accomplished as shown in Figure 23.3. 

We won t study the details of this substitution reaction until Chapter 11 but for now can picture it as happening by the pathway shown in Figure 8.6. The nucleophilic acetylide ion uses an electron pair to form a bond to the positively polarized, electrophilic carbon atom of bromomethane. As the new C-C bond forms, Br- departs, taking with it the electron pair from the former C-Br bond and yielding propyne as product. We call such a reaction an alkylation because a new alkyl group has become attached to the starting alkyne. 

Two different approaches are commonly used for the synthesis of alkynes. In the first, an appropriate electrophile undergoes nucleophilic attack by an acetylide ion. The electrophile may be an unhindered primary alkyl halide (undergoes Sn2), or it may be a carbonyl compound (undergoes addition to give an alcohol). Either reaction joins two fragments and gives a product with a lengthened carbon skeleton. This approach is used in many laboratory syntheses of alkynes. 

Explain why alkynes are more acidic than alkanes and alkenes. Show how to generate nucleophilic acetylide ions and use them in syntheses. 

Isomerization also results when sodium amide is used as the base in the double dehydrohalogenation. All possible triple-bond isomers are formed, but sodium amide is such a strong base that it deprotonates the terminal acetylene, removing it from the equilibrium. The acetylide ion becomes the favored product. When water is added to quench the reaction, the acetylide ion is protonated to give the terminal alkyne. 

Figure 7.94 adds several reactions to the ones we have discussed specifically. For example, it sneaks in a brand-new synthesis of substituted alkynes by using the acetylide ion as a nucleophile (usually effective only with primary R—L compounds). We mentioned the acidity of acetylenes in Chapter 3 (p. 129) and even... 

PROBLEM 10.65 Recall that terminal alkynes are among the most acidic of the hydrocarbons (p. 129), and that the acetylide ions can be used in 8 2 alkylation reactions with an appropriate aUgrl halide. For example. 

For example, NH2 is a stronger base than the acetylide ion that is formed, because NH3 (pA a = 36) is a weaker acid than a terminal alkyne (p Tg = 25). Recall that the weaker acid has the stronger conjugate base. Therefore, an amide ion ( NH2) can be used to remove a proton from a terminal alkyne to prepare an acetylide ion. 

In the remainder of this chapter, particular reactions are selected for examination of their synthetic potential. Acetylide ions are useful for linking carhon chains, particularly where a double bond is desired with stereoselectivity. Acetylene and 1-alkynes may be deprotonated with strong bases such as LDA and then treated with alkyl halides or carbonyl compounds. Preformed lithium acetylide complexed with ethylenediamine is available as a dry powder. Several alkynes derived from acetylide and carbon dioxide or formaldehyde are available, including propargyl alcohol (HC CCHjOH), propargyl bromide (HC CCH Br), and methyl propio-late (HC=CC02CH3). 

Now we need to make the alkyne needed in the above hydrogenation. The starting material provided lacks the butyl group at the triple bond. To attach the alkyl group, we can perform a nucleophilic substitution at 1-bromobutane with the acetylide ion generated from the starting material, by using sodium amide ... 

The acidic acetylenes react with certain heavy metal ions, chiefly Ag" and Cu, to form insoluble acetylides. Formation of a precipitate upon addition of an alkyne to a solution of AgN03 in alcohol, for example, is an indication of hydrogen attached to triply-bonded carbon. This reaction can be used to differentiate terminal alkynes (those with the triple bond at the end of the chain) from nonterminal alkynes. 

C(l)-Alkynylated tetrahydroquinolines (160) have been prepared from tettahydro-quinoline, an aldehyde (R -CHO) and an alkyne (R -C=C-H), using copper(I) iodide at 50 °C in toluene. The first two components are proposed to form an ejto-iminium ion in situ, which isomerizes to the n<7o-iminium, which then adds copper acetylide. 

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