When the acetylide is formed from
acetylene (HC≡CH), the reaction gives an α-
ethynyl alcohol. This process is often referred to as ethynylation. Such processes often involve metal
acetylide intermediates.
Scope
The principal reaction of interest involves the addition of the
acetylene (HC≡HR) to a
ketone (R2C=O) or
aldehyde (R−CH=O):
The reaction proceeds with retention of the
triple bond. For aldehydes and unsymmetrical ketones, the product is
chiral, hence there is interest in asymmetric variants. These reactions invariably involve metal-
acetylide intermediates.
This reaction was discovered by chemist
John Ulric Nef in 1899 while experimenting with reactions of elemental
sodium,
phenylacetylene, and
acetophenone.[3][4] For this reason, the reaction is sometimes referred to as
Nef synthesis. Sometimes this reaction is erroneously called the Nef reaction, a name more often used to describe a different reaction (see
Nef reaction).[1][3][5] Chemist
Walter Reppe coined the term ethynylation during his work with acetylene and carbonyl compounds.[1]
The Isler modification is a modification of Arens–Van Dorp Synthesis where ethoxyacetylene is replaced by
β-chlorovinyl ethyl ether and
lithium amide.[8]
Catalytic variants
Alkynylations, including the asymmetric variety, have been developed as metal-catalyzed reactions.[10][1] Various catalytic additions of alkynes to electrophiles in water have also been developed. [11]
Grignard reagents of acetylene or alkynes can be used to perform alkynylations on compounds that are liable to
polymerization reactions via enolate
intermediates. However, substituting
lithium for
sodium or
potassium acetylides accomplishes similar results, often giving this route little advantage over the conventional reaction.[1]
These reactions are used to manufacture
propargyl alcohol and
butynediol.[15] Alkali metal acetylides, which are often more effective for ketone additions, are used to produce 2-methyl-3-butyn-2-ol from acetylene and
acetone.
^
abMidland, M. Mark; Tramontano, Alfonso; Cable, John R. (1980). "Synthesis of alkyl 4-hydroxy-2-alkynoates". The Journal of Organic Chemistry. 45 (1): 28–29.
doi:
10.1021/jo01289a006.
^Li, C.-J. (2010). "The development of catalytic nucleophilic additions of terminal alkynes in water". Acc. Chem. Res. 43 (4): 581–590.
doi:
10.1021/ar9002587.
PMID20095650.
^Sondheimer, Franz; Rosenkranz, G.; Miramontes, L.; Djerassi, Carl (1954). "Steroids. LIV. Synthesis of 19-Nor-17α-ethynyltestosterone and 19-Nor-17α-methyltestosterone". Journal of the American Chemical Society. 76 (16): 4092–4094.
doi:
10.1021/ja01645a010.
^Hershberg, E. B.; Oliveto, Eugene P.; Gerold, Corinne; Johnson, Lois (1951). "Selective Reduction and Hydrogenation of Unsaturated Steroids". Journal of the American Chemical Society. 73 (11): 5073–5076.
doi:
10.1021/ja01155a015.
^Coffman, Donald D. (1940). "Dimethylethhynylcarbinol". Organic Syntheses. 40: 20.
doi:
10.15227/orgsyn.020.0040.
^Sobenina, L. N.; Tomilin, D. N.; Petrova, O. V.; Mikhaleva, A. I.; Trofimov, B. A. (2013). "Synthesis of secondary propargyl alcohols from aromatic and heteroaromatic aldehydes and acetylene in the system KOH-H2O-DMSO". Russian Journal of Organic Chemistry. 49 (3): 356–359.
doi:
10.1134/S107042801303007X.
S2CID94135082.