Condensation with carbonyl compounds

Acetylene is condensed with carbonyl compounds to give a wide variety of products, some of which are the substrates for the preparation of families of derivatives. The most commercially significant reaction is the condensation of acetylene with formaldehyde. The reaction does not proceed well with base catalysis which works well with other carbonyl compounds and it was discovered by Reppe (33) that acetylene under pressure (304 kPa (3 atm), or above) reacts smoothly with formaldehyde at 100°C in the presence of a copper acetyUde complex catalyst. The reaction can be controlled to give either propargyl alcohol or butynediol (see Acetylene-DERIVED chemicals). 2-Butyne-l,4-diol, its hydroxyethyl ethers, and propargyl alcohol are used as corrosion inhibitors. 2,3-Dibromo-2-butene-l,4-diol is used as a flame retardant in polyurethane and other polymer systems (see Bromine compounds Elame retardants). 

A small amount of acetylene is used in condensations with carbonyl compounds other than formaldehyde. The principal uses for the resulting acetylenic alcohols are as intermediates in the synthesis of vitamins (qv). 

Silyloxy esters.l Silyl ketene acetals are known to undergo aldol condensation with carbonyl compounds in the presence of TiCl4 (12,268) to afford (3-silyloxy esters. The same products can be obtained in a one-step reaction of an a,p-unsaturated ester with trimethylsilane and a carbonyl compound in the presence of RhCl3H20. 

Various nitro compounds have been condensed with carbonyl compounds in reactions catalyzed by alkaline earth metal oxides and hydroxides 145). It was found that the reactivities of the nitro compounds were in the order nitro-ethane > nitromethane > 2-nitropropane, and those of carbonyl compounds were propionaldehyde > isobutyraldehyde > pivalaldehyde > acetone > benzaldehyde > methyl propionate. Among the catalysts examined, MgO, CaO, Ba(OH)2, and Sr(OH)2, exhibited high activity for nitroaldol reaction of nitromethane with propionaldehyde. In reactions with these catalysts, the yields were between 60% (for MgO) and 26% (for Sr(OH)2) at 313 K after 1 h in a batch reactor. On Mg(OH)2, Ca(OH)2, and BaO, the yields were in the range of 3.8% (for BaO) and 17.5% (for Mg(OH)2). Investigation of the influence of the pre-treatment... 

Hydrazinolysis products obtained from oxazolones 528 are versatile synthetic intermediates and can be further elaborated to a variety of different heterocycles depending on the substituents and on the experimental conditions. For example, N-aminoimidazolones 529, isolated from reaction of 528 and hydrazine, have been acylated ° or condensed with carbonyl compounds to produce 530 and 531, respectively. On the other hand, ring-opening 528 with hydrazine affords a dehydroamino acid hydrazide 532. Condensation of 532 with aldehydes yields a hydrazone 533 that can be cyclized to an A -iminoimidazolone 534 (Scheme 7.168). ... 

Condensations with carbonyl compounds phenol-formaldehyde resins. Acid or base catalyzes electrophilic substitution of carbonyl compounds in ortho and para positions of phenols to form phenol alcohols (Lederer-Manasse reaction). 

A wide variety of compounds having the primary amino group condense with carbonyl compounds to give )C=N— compounds by the elimination of water. The latter reactions are usually acid catalyzed because protonation of the carbonyl group enhances its reactivity toward nucleophilic attack by the amino group on the carbonyl carbon atom (Eq. 1). 

Organic hydrazines or diazanes are substitution products of NH2—NH2 and have many properties similar to those of amines in being basic and forming acyl derivatives as well as undergoing alkylation and condensations with carbonyl compounds (Section 16-4C). Unsymmetrical hydrazines can be prepared by careful reduction of /V-nitrosamines. l,l-Dimethyldiazane is prepared in this way for use as a rocket fuel ... 

Reaction XLIII. (c) Condensation of a-Halogen Fatty Acid Esters with Aldehydes and Ketones by means of Zinc or Magnesium (Reformatsky-Grignard). (C., (1901), I., 1196 II., 30 (1902), I., 856.)—This is an extension of the Grignard and zinc alkyl reactions which enables a-halogen esters to be condensed with carbonyl compounds as if they were simple alkyl halogen compounds. The zinc or magnesium alkyl derivative is neither prepared beforehand nor isolated in the reaction, but there is little doubt that some such compound is transitorily formed. Zinc is the metal... 

In summary, the SMS reaction is a truly efficient process, possessing a broad scope and applicable to a number of carbonyls, allylsilanes, alcohols (silyl ethers) or amines. Its usefulness has been validated in several total syntheses and demonstrated by the preparation of chiral homoallylic alcohols. During the development of the SMS reaction, Melkafia and Marko [48] realized that the homoallylic alcohol (ether), if connected to an allylsilane, would form novel annelating agents that would lead to tetrahydropyran derivatives via condensation with carbonyl compounds. This reaction was called IMSC for intramolecular Sakurai cydization and will be discussed in the next section. 

Jones, F. N. Vaulx, R. L. Hauser, C. R. o-Meta-lation of benzyldimethylamine and related amines with BuLi. Condensations with carbonyl compounds to form ortho derivatives. 

The intermediacy of such oxaspiropentanes has been proposed in the addition of diazomethane to ketonesi0) and in the reaction of dimethyloxosulfonium methylide with a-haloketones55). In contrast to phosphorous ylides, sulfur ylides usually condense with carbonyl compounds to yield epoxides, thus reaction of the N,N-dimethylaminophenyloxosulfonium cyclopropylide 99 with cyclohexanone produced the dispiroepoxide 100 which rearranged to the spiro [3.5] nonan-l-one 101 upon isolation by gas chromatography, Eq. (29) S6). 

Synthesis of N-heterocycles by condensation with carbonyl compounds... 

The amino acid synthesis from Strecker has been known since 1850 [25]. Stereoselective versions of this synthesis start with chiral amines, which are condensed with carbonyl compounds to form imines. Addition of hydrogen cyanide and subsequent hydrolysis of the amino nitriles yields the amino acids. When ketones are used for the condensation, a-alkylated amino acids are obtained in high yields and optical purities... 

The acidity of hydrogen atoms adjacent to the nitrogen substituent of N-nitrosamines has been known for many years, although Seebach and coworkers played a major role in developing this into a usefiil synthetic process. For example, the anion of N-nitrosodimethylamine is formed by using LDA, and can be alkylated or condensed with carbonyl compounds or nitriles (Scheme 2). l-Bromo-3-iodopropane... 

As with butadiyne, the sodium salts of the polyynes 79 which are present in the reaction mixture after dehydrohalogenation can be alkylated or condensed with carbonyl compounds. The resulting derivatives are more stable and can usually be obtained in somewhat higher yields than the parent polyynes, but the improvement is only slight in the pentaacetylene case, where, for example, the dimethyl derivative, CHsCC QsCHj, is obtained in 3% yield . 

In carbohydrate chemistry, condensatiMi with carbonyl compounds such as acetone, acetaldehyde, formaldehyde and benzaldehyde is of great importance for the protection of pairs of hydroxyl groups. Trityla-tion may also be used in these instances for the protection of individual primary hydroxyl groups before carrying out the condensation with carbonyl compounds. After the condensation, the individual hydroxyl groups may be liberated by suitable detritylation methods. As yet, these possibilities have been explored very little. Wolfrom and coworkers described the condensation of 1,6-ditrityldulcitol with benzaldehyde to l,6-ditrityl-2,3,4,5-dibenzylidenedulcitol. Acetals other than those obtained by direct condensation are thus available. 

Use of N-substituted 2-aminonitriles in the condensation with carbonyl compounds generates cyano-stabilized azomethine ylides (87BCJ4067). The reaction of benzaldehyde with (methylamino)acetonitrile leading to ylide 84 is an example. 

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