Amide, sodium reaction with Grignard reagents

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). 

Alternatives for the assembly of the a-aminocarbonyl-component in protected form include the reaction of a 2-bromo-ketone with sodium diformamide producing an a-formamido-ketone, and the reaction of a Weimeb amide of an A-Cbz a-amino acid with a Grignard reagent, the release of the A-protection in the presence of the second component, produces the pyrrole. ... 

Many examples of 4- or 5-acetyl-1,2,3-triazoIes have been prepared and a number of methods developed. For example, the addition of phenyl azide to acetylphenylacetylene (Eq. 14) gives an excellent yield, and both isomeric products are obtained. The reaction of sodium azide with /3-acetylstyrylsulfones proceeds in good yield (Eq. 15). The diacetyl phenylhydrazone 5.1-12 is smoothly converted to a 1,2,3-triazole under novel conditions that deserve further exploration (Eq. 16). The heterocyclic azide 5.1-13 reacts with 2,4-pentanedione under basic conditions (. 17). The treatment of the amides 5.1-14 with a Grignard reagent produces... 

This reaction was first reported by Bourguel in 1925. It is the synthesis of alkynes by the treatment of 2,3-dibromo-l-propene with a Grignard reagent to form a 3-substituted 2-bromo-l-propene, which further reacts with sodium amide. The yields are normally very high. Another advantage of using sodium amide in the last step is that other internal alkynes can isomerize to terminal alkynes. ... 

Several improvements in acylation techniques were announced. Butyllithium wwas determined to be superior to sodium amide in preparation of amide ions for ammonolysis reactions with esters. Phosgene is more reactive than ethyl chloroformate toward eneamines. The intermediate acyl chlorides may then be converted to a variety of products. a-Acetylenic aldehydes are easily prepared by the action of acetylenic Grignard reagents upon ethyl formate. ... 

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. 

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