Ethynylation

CONDENSATIONS WITH SODAMIDE IN LIQUID AMMONIA Acetylenic compounds are conveniently prepared with the aid of Uquid ammcx as a solvent. The preparation of a simple acetylenic hydrocarbon ( -butylacetylene or 1-hexyne) and also of phenylacetylene is described. Experimental details are also given for two acetylenic carbinols, viz., 1-ethynyl-eyciohoxanul and 4-pentyn-l-ol. It will be noted that the scale is somewhat laige smaller quantities can readily be prepared by obvious modifications of the directions. 

The synthesis of spiro compounds from ketones and methoxyethynyl propenyl ketone exemplifies some regioselectivities of the Michael addition. The electrophilic triple bond is attacked first, next comes the 1-propenyl group. The conjugated keto group is usually least reactive. The ethynyl starting material has been obtained from the addition of the methoxyethynyl anion to the carbonyl group of crotonaldehyde (G. Stork, 1962 B, 1964A). 

The (l-ethynyl)-2-propenyl acetate derivative 111 undergoes an interesting PdCl2(PhCN)2-catalyzed cyclization to form the 2-cyclopentenone 112[47], A Pd-carbene complex is assumed to be an intermediate of the formation of 112. 

When the —C=CH group is named as a substituent it is designated as an ethynyl... 

The name ethynylation was coined by Reppe to describe the addition of acetylene to carbonyl compounds (8). 

Although stoichiometric ethynylation of carbonyl compounds with metal acetyUdes was known as early as 1899 (9), Reppe s contribution was the development of catalytic ethynylation. Heavy metal acetyUdes, particularly cuprous acetyUde, were found to cataly2e the addition of acetylene to aldehydes. Although ethynylation of many aldehydes has been described (10), only formaldehyde has been catalyticaHy ethynylated on a commercial scale. Copper acetjlide is not effective as catalyst for ethynylation of ketones. For these, and for higher aldehydes, alkaline promoters have been used. 

Butynediol. Butynediol, 2-butyne-l,4-diol, [110-65-6] was first synthesized in 1906 by reaction of acetylene bis(magnesium bromide) with paraformaldehyde (43). It is available commercially as a crystalline soHd or a 35% aqueous solution manufactured by ethynylation of formaldehyde. Physical properties are Hsted in Table 2. 

Ma.nufa.cture. AU. manufacturers of butynediol use formaldehyde ethynylation processes. The earliest entrant was BASF, which, as successor to I. G. Farben, continued operations at Ludwigshafen, FRG, after World War II. Later BASF also set up a U.S. plant at Geismar, La. The first company to manufacture in the United States was GAF in 1956 at Calvert City, Ky., and later at Texas City, Tex., and Seadrift, Tex. The most recent U.S. manufacturer is Du Pont, which went on stream at La Porte, Tex., about 1969. Joint ventures of GAF and Hbls in Mad, Germany, and of Du Pont and Idemitsu in Chiba, Japan, are the newest producers. 

Secondary acetylenic alcohols are prepared by ethynylation of aldehydes higher than formaldehyde. Although copper acetyUde complexes will cataly2e this reaction, the rates are slow and the equiUbria unfavorable. The commercial products are prepared with alkaline catalysts, usually used in stoichiometric amounts. 

Ethynylation of ketones is not cataly2ed by copper acetyUde, but potassium hydroxide has been found to be effective (180). In general, alcohols are obtained at lower temperatures and glycols at higher temperatures. Most processes use stoichiometric amounts of alkaU, but tme catalytic processes for manufacture of the alcohols have been described the glycols appear to be products of stoichiometric ethynylation only. 

Methylbutynol. 2-Methyl-3-butyn-2-ol [115-19-5] prepared by ethynylation of acetone, is the simplest of the tertiary ethynols, and serves as a prototype to illustrate their versatile reactions. There are three reactive sites, ie, hydroxyl group, triple bond, and acetylenic hydrogen. Although the triple bonds and acetylenic hydrogens behave similarly in methylbutynol and in propargyl alcohol, the reactivity of the hydroxyl groups is very different. 

Ethynyl carbinols rearrange to conjugated unsaturated aldehydes. Copper or silver salts cataly2e isomeri2ation of the acetate to an aHenic acetate, which can be hydroly2ed to an unsaturated aldehyde (204). 

Unlike ethynylation, in which acetylene adds across a carbonyl group and the triple bond is retained, in vinylation a labile hydrogen compound adds to acetylene, forming a double bond. 

Ethynylation. Base-catalyzed addition of acetylene to carbonyl compounds to form -yn-ols and -yn-glycols (see Acetylene-DERIVED chemicals) is a general and versatile reaction for the production of many commercially useful products. Finely divided KOH can be used in organic solvents or Hquid ammonia. The latter system is widely used for the production of pharmaceuticals and perfumes. The primary commercial appHcation of ethynylation is in the production of 2-butyne-l,4-diol from acetylene and formaldehyde using supported copper acetyHde as catalyst in an aqueous Hquid-fiHed system. 

The ethynylation reaction takes place at 10—40°C and 2 MPa (20 atm) and hquid ammonia is the solvent. The methylbutynol is converted into methylbutenol by selective hydrogenation and then is dehydrated over alumina at 250—300°C. Polymerization-grade isoprene is obtained. 

Stabilized lithium acetyhde is not pyrophoric or shock-sensitive as are the transition-metal acetyhdes. Among its uses are ethynylation of halogenated hydrocarbons to give long-chain acetylenes (132) and ethynylation of ketosteroids and other ketones in the pharmaceutical field to yield the respective ethynyl alcohols (133) (see Acetylene-derived chemicals). 

Lithium acetyhde also can be prepared directly in hquid ammonia from lithium metal or lithium amide and acetylene (134). In this form, the compound has been used in the preparation of -carotene and vitamin A (135), ethchlorvynol (136), and (7j--3-hexen-l-ol (leaf alcohol) (137). More recent synthetic processes involve preparing the lithium acetyhde in situ. Thus lithium diisopropylamide, prepared from //-butyUithium and the amine in THF at 0°C, is added to an acetylene-saturated solution of a ketosteroid to directly produce an ethynylated steroid (138). 

Diol Components. Ethylene glycol (ethane 1,2-diol) is made from ethylene by direct air oxidation to ethylene oxide and ring opening with water to give 1,2-diol (40) (see Glycols). Butane-1,4-diol is stiU made by the Reppe process acetylene reacts with formaldehyde in the presence of catalyst to give 2-butyne-l,4-diol which is hydrogenated to butanediol (see Acetylene-DERIVED chemicals). The ethynylation step depends on a special cuprous... 

Reaction of an acid chloride with trimethylsilylacetylene produces an a,P-ethynyl ketone, which on treatment with substituted hydrazines yields a mixture of 1,5- and 1,3-substituted pyrazoles (34). The ratio is dependent on the reaction conditions (eq. 3). 

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