Aldehydes acetylene addition

Our first goal was to develop a scaleable route to the single enantiomer propargylic alcohol. The racemic alcohol was readily produced on a multi-kilogram scale by alkylation of the phenol with inexpensive bromoacetaldehyde diethyl acetal, hydrolysis to the aldehyde, and addition of the acetylenic Grignard reagent. With this material at hand we developed an efficient bioresolution process that esterified the alcohol in the presence of Chirazyme L9 (Scheme 30.7).26 At this point... 

Reaction of aliphatic aldehydes with alkali acetylides in liquid ammonia gives the carbinols in very small amounts, even when the aldehyde is added to a strongly cooled solution of lithium acetylide. The predominant reaction presumably is formation of the enolate and the aldol condensation product As shown on p. 21, a suspension of LiOCH in THF can be obtained by gradually replacing the ammonia of an ammoniacal solution of the acetylide by THF. The lithium acetylide obtained in this way probably thanks its stability to the complexed ammonia. In the procedure described below, butanal is added to the suspension to give the acetylenic carbinol in a reasonable yield. Since this compound is rather volatile, it is essential to remove the greater part of the THF, before the hydrolysis is carried out. The main solvent which then has to be removed in the isolation procedure is the diethyl ether, used for the extractions. During the addition of the aldehyde, acetylene is introduced to suppress the formation of the diol RCH(OH)C=CCH(OH)R. 

Addition of HCN to unsaturated compounds is often the easiest and most economical method of making organonitnles. An early synthesis of acrylonitrile involved the addition of HCN to acetylene. The addition of HCN to aldehydes and ketones is readily accompHshed with simple base catalysis, as is the addition of HCN to activated olefins (Michael addition). However, the addition of HCN to unactivated olefins and the regioselective addition to dienes is best accompHshed with a transition-metal catalyst, as illustrated by DuPont s adiponitrile process (6—9). 

Acetaldehyde [75-07-0] (ethanal), CH CHO, was first prepared by Scheele ia 1774, by the action of manganese dioxide [1313-13-9] and sulfuric acid [7664-93-9] on ethanol [64-17-5]. The stmcture of acetaldehyde was estabhshed in 1835 by Liebig from a pure sample prepared by oxidising ethyl alcohol with chromic acid. Liebig named the compound "aldehyde" from the Latin words translated as al(cohol) dehyd(rogenated). The formation of acetaldehyde by the addition of water [7732-18-5] to acetylene [74-86-2] was observed by Kutscherow] in 1881. 

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. 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

Solutions of RC triple-bond C—Ti(0-/-C2H2)2 can be prepared by treating acetylenic compounds, such as phenylacetylene, with butyl lithium and then Cl—Ti(0-/-C2H2)2. These materials can react with aldehydes and epoxides to give the expected addition products (215). 

Hydrogen bromide adds to acetylene to form vinyl bromide or ethyHdene bromide, depending on stoichiometry. The acid cleaves acycHc and cycHc ethers. It adds to the cyclopropane group by ring-opening. Additions to quinones afford bromohydroquinones. Hydrobromic acid and aldehydes can be used to introduce bromoalkyl groups into various molecules. For example, reaction with formaldehyde and an alcohol produces a bromomethyl ether. Bromomethylation of aromatic nuclei can be carried out with formaldehyde and hydrobromic acid (6). 

These reactions ate carried out in the presence of acidic and basic catalysts. The acid-cataly2ed addition of ethyl alcohol to acetylene or to a vinyl ether produces acetals (diethers of 1,1-dihydroxyethane). The acid-cataly2ed reaction of ethyl alcohol with an aldehyde or ketone also gives acetals. 

Electrochemically generated trifluoromethyl radicals add to 1-hexyne to give a 1 4 mixture of ( )- and (Z)-l,l,l-trifluoro-2-heptene [22] Kinetic data on the addition of photochemically generated trifluoromethyl radicals to acetylene and substituted acetylenes were reported [2J]. Alcohols and aldehydes add to hexa-fluoro-2-butyne in the presence of peroxide and y-ray initiation [24] (equations 16 and 17). 

Dicarbomethoxyacetylene has also been added to the pyrrolidine enamine derivative of acetylacetone, demonstrating a new synthesis of phthalic esters (345). A 3-acylpyridine synthesis was achieved by the addition of an acetylenic aldehyde to the vinylogous amide derived from ammonia and dihydroresorcinol (346). 

Disubstituted isotellurazoles 1 (4-11%) and bis((3-acylvinyl)tellurides 3 (3-10%) were isolated in very low yields from the reaction mixture as the products of nucleophilic addition of telluride anion to the triple bond of the initial ethynyl ketones (83S824). This method cannot be applied to the synthesis of 3//-isotellurazoles. When a-acetylenic aldehydes were used instead of ethynyl ketones, bis((3-cyanovinyl)tellurides 4 obtained in 14-20% yields were the only products (83S824). 

The hydration of triple bonds is generally carried out with mercuric ion salts (often the sulfate or acetate) as catalysts. Mercuric oxide in the presence of an acid is also a common reagent. Since the addition follows Markovnikov s rule, only acetylene gives an aldehyde. All other triple-bond compounds give ketones (for a method of reversing the orientation for terminal alkynes, see 15-16). With allqmes of the form RC=CH methyl ketones are formed almost exclusively, but with RC=CR both possible products are usually obtained. The reaction can be conveniently carried out with a catalyst prepared by impregnating mercuric oxide onto Nafion-H (a superacidic perfluorinated resinsulfonic acid). ... 

Similar reactions have been carried out on acetylene. Aldehydes add to alkynes in the presence of a rhodium catalyst to give conjugated ketones. In a cyclic version of the addition of aldehydes, 4-pentenal was converted to cyclopen-tanone with a rhodium-complex catalyst. In the presence of a palladium catalyst, a tosylamide group added to an alkene unit to generate A-tosylpyrrolidine derivatives. ... 

Although the unsaturated nitrile oxides 124 can be prepared via the aldoxime route (see Scheme 8), the older procedure suffers from the disadvantage that a tenfold excess of allyl alcohol and two additional steps are required when compared to Scheme 15. Therefore, unsaturated nitro ether 123 that can be prepared by condensation of an aldehyde 120 and a nitro alkane followed by Michael addition of alcohol 122, was a useful precursor to nitrile oxide 124 [381. The nitrile oxide 124 spontaneously cyclized to ether 125. This procedure is particularly suitable for the synthesis of tetrahydrofurans (125a-h) and tetrahydropyrans (125i-k) possessing Ar substituents in 72-95% yield (Table 12). The seven-membered ether 1251 was obtained only in 30% yield on high dilution. The acetylenic nitro ether 126 underwent INOC reaction to provide the isoxazole 127. 

By analogy, the acetylene aldehyde 500 gives, on addition of the chiral Li-enolate 501 [79-82], the chiral //-lactams 502 and 503 in 75% yield [80-82]. Similar (fhc-tam-forming reactions are discussed elsewhere [70, 83-88]. The ketone 504 affords, with the lithium salt of the silylated lithium amide 505, the Schiff base 506, in 74% yield (Scheme 5.27). The Schiff base 506 is also obtained in 25% yield by heating ketone 504 with (C6H5)3P=N-C6H4Me 507 in boiling toluene for 7 days... 

The facility with which the transfer of acetylenic groups occurs is associated with the relative stability of the ip-hybridized carbon. This reaction is an alternative to the more common addition of magnesium or lithium salts of acetylides to aldehydes. 

Corrosion of steel during oil well acidizing or acid pickling treatments can be controlled effectively and economically with organic corrosion inhibitors. These additives interact with the steel surface to form an adherent barrier, the nature of which depends on the additives physicochemical properties. Work to date has established that acetylenic alcohols chemisorb and subsequently polymerize on steel surfaces (1-5"). a,/MJnsaturated aldehydes and a-alkenyl-phenones appear to behave in a similar manner (6j7"). The nature of Current address Amoco Production Company, Tulsa, OK... 

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