Aldehyde synthesis reaction

Aromatic hydrocarbons and aryl halides can be converted into sulfinic acids in yields averaging 80% if the reaction is carried out at low temperature, if, as in the Gattermann aldehyde synthesis, reaction is initiated by passing in dry hydrogen chloride, and if the tetrachloroaluminum sulfinate formed is decomposed, not by acid, but by alkali, and acid is used for the first time to decompose the alkali sulfinites thus formed.240 Aryl ethers give sulfinic acids even in the cold, but reaction readily proceeds further to give sulfoxides and sulfonium compounds 241... 

Hoesch synthesis A variation of the Gattermann synthesis of hydroxy-aldehydes, this reaction has been widely applied to the synthesis of anthocyanidins. It consists of the condensation of polyhydric phenols with nitriles by the action of hydrochloric acid (with or without ZnCl2 as a catalyst). This gives an iminehydrochloride which on hydrolysis with water gives the hydroxy-ketone. 

Aldehydes by reaction with ammonia and cyanide ion (the Strecker synthesis)... 

Aromatic and heterocycHc compounds are formylated by reaction with dialkyl- or alkylarylformamides in the presence of phosphoms oxychloride or phosgene (Vilsmeier aldehyde synthesis) (125). The Vilsmeier reaction is a Friedel-Crafts type formylation (126), since the intermediate cation formed by the interaction of phosphoms oxychloride with formamide is a typical electrophilic reagent. Ionic addition compounds of formamide with phosgene or phosphoms oxychloride are also known (127). 

The Gattermann-Koch reaction when appHed to alkenes or alkanes gives ketones or acids but not aldehydes. However, the Vilsmeier aldehyde synthesis can be appHed to aUphatic compounds. For example, 1,2-diaLkoxyethylenes react with /V-methy1foTmani1ide and POCl to give alkoxymalondialdehydes ... 

Alpha amino acids (and aldehydes) synthesis by reaction of an alpha keto add with another amino acid (Herbst-EngeO or by reaction of a keto acid with ammonia tmdef reducing conditions (Knoop-Oe sterling). 

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

A third method of aldehyde synthesis is one that we ll mention here just briefly and then return to in Section 21.6. Certain carboxylic acid derivatives can be partially reduced to yield aldehydes. The partial reduction of an ester by dhsobutylaluminum hydride (DIBAH), for instance, is an important laboratory-scale method of aldehyde synthesis, and mechanistically related processes also occur in biological pathways. The reaction is normally carried out at —78 °C (dry-ice temperature) in toluene solution. 

It is interesting to speculate that asymmetric induction may be the consequence of the exo anomeric effect, a stereoelectronic effect that favors the conformation 5 that places the aglycone O-C bond antiperiplanar to the pyran C(1) —C(2) bond7fi. Related asymmetric induction has also been observed in aldehyde addition reactions of the related, but racemic, pinacol (Z)-y-(tetrahydropyranyloxy)allylboronate49. As indicated in the examples above, however, the level of diastereoselectivity is modest and the only application in asymmetric synthesis is Wuts exo-brevicomin synthesis75. 

Ring contractions, such as the Tavorskii reaction on (38), or the cyclopentane aldehyde synthesis on p 374... 

Photocatalytic oxidation is a novel approach for the selective synthesis of aldehyde and acid from alcohol because the synthesis reaction can take place at mild conditions. These reactions are characterized by the transfer of light-induced charge carriers (i.e., photogenerated electron and hole pairs) to the electron donors and acceptors adsorbed on the semiconductor catalyst surface (1-4). Infrared (IR) spectroscopy is a useful technique for determining the dynamic behavior of adsorbed species and photogenerated electrons (5-7). 

Entry 2 involves the use of a sterically biased enol boronate with an a-substituted aldehyde. The reaction, which gives 40 1 facial selectivity, was used in the synthesis of 6-deoxyerythronolide B and was one of the early demonstrations of the power of double diastereoselection in synthesis. In Entry 3, the syn selectivity is the result of a chelated TS, in which the (3-p-methoxybenzyl substituent interacts with the tin ion.120... 

Hydroxymethylation (formaldehyde) of nitro-imidazole 76 affords 77, which is oxidized to aldehyde 78. To prepare the other fragment for this convergent synthesis, reaction of epichlorohydrin with morpholine leads to the aminoepoxide 79, which is reacted with hydrazine to afford 80. Reaction of this substituted hydrazine with dimethyl carbonate affords oxazolinone 81 by sequential ester interchange reactions. Condensation of 81 with aldehyde 78 affords the antitricho-... 

The spirobenzylisoquinoline 171b derived from berberine (15) (Section IV,A,1) was oxidized with m-chloroperbenzoic acid to the /V-oxide 389, which was treated with trifluoroacetic anhydride to afford dehydrohydrastine (370) in 56% overall yield (Scheme 71) through the Polonovski reaction (187). Holland et al. (188,189) reported the reverse reaction from dehydrophthalides to spirobenzylisoquinolines, namely, 370 was reduced with diisobutylalu-minum hydride to give a mixture of two diastereoisomeric spirobenzylisoquinolines 320 and 348 via the enol aldehyde. This reaction was applied to synthesis of various spirobenzylisoquinoline alkaloids such as (+)-sibiricine (352), ( + )-corydaine (347), (+ )-raddeanone (354), ( )-yenhusomidine (359), (+ )-ochrobirine (343), and ( )-yenhusomine (323). 

Numerous other aldehyde condensation reactions of five-membered heterocycles have been utilized in the synthesis of the central pyridine core. Paulmier and co-workers employed the condensation of 3-aminothiophenes 114 with aldehydes to give bis-thiophenylpyridines 115 (Equation 25) <1996JHC9>. 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

The synthesis shown in Fig. 40 provided access to heptoses,55 but according to our definition, this is not a higher sugar synthesis. However, the approach to such derivative was based on the Baylis-Hillman reaction of acyclic sugar-derived aldehydes, a reaction not commonly applied in sugar chemistry and worth to mention in this review. 

The range of the reaction was extended by the elegant aldehyde synthesis of Gattermann and Koch. If a mixture of carbon monoxide and hydrogen chloride is allowed to act in the presence of aluminium chloride (and cuprous chloride) on toluene (benzene is less suitable), the reaction occurs which might he expected with formyl chloride if this substance were capable of existence. 

The aldehyde-aldehyde aldol reactions were first nsed in a natural product synthesis setting by Pihko and Erkkila, who prepared prelactone B in only three operations starting from isobutyraldehyde and propionaldehyde (Scheme 40). Crossed aldol reaction under proline catalysis, followed by TBS protection, afforded protected aldehyde 244 in >99% ee. A highly diastereoselective Mukaiyama aldol reaction and ring closure with aqueous HE completed the synthesis [112]. 

In a one-step synthesis problem, you know that only one reaction is necessary to form a particular product. The key is the functional group in that product. For example, if the functional group is an aldehyde, the reaction must be one of the limited number of reactions that you know form an aldehyde. Other information may limit your choice of reactions. For example, the problem may ask you to begin with an alcohol with the same number of carbon atoms, or you may have an alkene with a greater number of Ccirbon atoms. 

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