Ethynylation of formaldehyde

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. 

Ethynylation of formaldehyde is the major route for the commercial manufacture of 1,4—butynediol. This process is also known as the Reppe process. The stoichiometric reaction for this process is ... 

Complex reactions with consecutive or parallel steps are commonly encountered in catalytic slurry reactors, e.g. in hydration of propylene oxide, ethynylation of formaldehyde to bu-tinediol or hydrogenation of unsatturated oils [35, 36, 37, 38, 39]. If one can assume in a simplified analysis of these reactions that the concentrations of the liquid reactants are in excess, compared to the gaseous one (Aj ) the rate of reaction of the gaseous reactant (in the absence of intraparticle diffusion) can be expressed as... 

C3 Ethynylation of formaldehyde Butynediol Copper acetylide Fine chemicals [32]... 

For conditions where this criterion and Equations (69) are satisfied, Chaudhari and Ramachandran recently published design equations taking the internal particle diffusion effects into account [l58]. They applied this model to the hydrogenation of DNT, the ethynylation of formaldehyde and the oxidation of cyclohexene. Fig. 28 shows the influence of pressure on the conversion rate. The decrease in ("R ) below a critical pressure indeed could be predicted by this model within 23%. A complication not accounted for... 

Fig. 28 Influence of pressure on rate of ethynylation of formaldehyde (B) in a slurry reactor explained by a model for mass transfer with zero order reaction.

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. 

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. Condensation of acetylene with a reagent such as aldehyde to yield an acetylenic derivative. The best example is the union of formaldehyde and acetylene to produce butyne-diol, H0-CH2.C C.CH2.0H Ref CondChemDict (1961), 478-R 8th edit (1971), 375-R... 

Schaffer398 described a synthesis of L-apiose by reaction of 170 with formaldehyde, and Horton et al,373 developed a method for extension of sugar chains through ethynylation of 170 and other aldehydo compounds by the Grignard reaction. 

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. 

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. 

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... 

Dj Ethynylation Reaction of acetylene with formaldehyde over a CaCf-supported catalyst. 

All manufacturers of butynediol use this formaldehyde ethynylation process, and yields of butynediol may be in excess of 90 percent, in addition to 4 to 5% propargyl alcohol. 

In order to synthesize alkyne 223, enantioenriched ethynylaziridme 220 was prepared by a known four-step sequence (762) from (S)-Gamer s aldehyde (765,164). A reductive coupling reaction (765,166) of the aziridine 220 with formaldehyde in the presence of Pd(Ph3)4 and Inl furnished the 2-ethynyl-l,3-amino alcohol 221. Protection of 221 as benzylidene acetal gave the alkyne 222, which was converted in the next step to the corresponding iodoalkyne 223 (767). 

The alternative synthesis of (-)-norgestrel (Fig. 30) at Sobering AG [36] makes use of an enantioselective Robinson annotation [37]. Starting from methylvinylketone and 2-ethylcyclopenta-l,3-dione (D), in the presence of L-proline (A), one reaches the optically active CD-intermediate. Formaldehyde and the substituted ethyl acetoacetate shown provide the missing carbon atoms. From the BCD-intermediate to the ABCD-diketone is only a short distance. Partial and site specific addition of the ethynyl group completes a lucid synthesis. 

By use of the versatile reactivity of the copper catalysts, the Ohno group expanded their three-component indole formation (Scheme 19.78) to a one-pot synthesis of diazepine-fused indoles [152]. After formation of 2-(aminomethyl)indoles 307 using 2-ethynyl-At-mesylanilines 305, formaldehyde, and 2-bromobenzylamines 288b, addition of NaOMe furnishes removal of Ms group and spontaneous copper-catalyzed N-arylation to produce indole-fused 1,4-diazepines 308 (Scheme 19.82). 

---