Aldehydes from carbonyl chlorides

Epoxidation of aldehydes and ketones is the most profound utility of the Corey-Chaykovsky reaction. As noted in section 1.1.1, for an a,P-unsaturated carbonyl compound, 1 adds preferentially to the olefin to provide the cyclopropane derivative. On the other hand, the more reactive 2 generally undergoes the methylene transfer to the carbonyl, giving rise to the corresponding epoxide. For instance, treatment of P-ionone (26) with 2, derived from trimethylsulfonium chloride and NaOH in the presence of a phase-transfer catalyst Et4BnNCl, gave rise to vinyl epoxide 27 exclusively. ... 

A viable iron carbonyl-mediated reduction process converts acid chlorides and bromoalkanes into aldehydes [3, 6]. Yields are high, with the exception of nitro-benzoyl chloride, and the procedure is generally applicable for the synthesis of alkyl, aryl and a,(i-unsaturated aldehydes from the acid chlorides. The reduction proceeds via the initial formation of the acyl iron complex, followed by hydride transfer and extrusion of the aldehyde (cf. Chapter 8). 

On the pages which follow, general methods are illustrated for the synthesis of a wide variety of classes of organic compounds including acyl isocyanates (from amides and oxalyl chloride p. 16), epoxides (from reductive coupling of aromatic aldehydes by hexamethylphosphorous triamide p. 31), a-fluoro acids (from 1-alkenes p. 37), 0-lactams (from olefins and chlorosulfonyl isocyanate p. 51), 1 y3,5-triketones (from dianions of 1,3-diketones and esters p. 57), sulfinate esters (from disulfides, alcohols, and lead tetraacetate p. 62), carboxylic acids (from carbonylation of alcohols or olefins via carbonium-ion intermediates p. 72), sulfoxides (from sulfides and sodium periodate p. 78), carbazoles... 

The ethylidene, or unsymmetrical di-halogen substitution products of ethane, are not of much importance, because they do not easily undergo reaction. They are prepared by the reactions just described, viz., from aldehyde by the action of phosphorus penta-chloride, -bromide, or -iodide. Also by the action of phosphorus chlor-bromide, PCl3Br2, or of carbonyl chloride (phosgene), COCI2. They may also be made by the further halogenation of the mono-halogen ethanes ... 

From a historical perspective, the a-(dialkylamino)nitrile anions were the first acyl anion equivalents to undergo systematic investigation. More recent studies indicate that anions of a-(dialkylamino)nitriles derived from aliphatic, aromatic or heteroaromatic aldehydes intercept an array of electrophiles including alkyl halides, alkyl sulfonates, epoxides, aldehydes, ketones, acyl chlorides, chloroformates, unsaturated ketones, unsaturated esters and unsaturated nitriles. Aminonitriles are readily prepared and their anions are formed with a variety of bases such as sodium methoxide, KOH in alcohol, NaH, LDA, PhLi, sodium amide, 70% NaOH and potassium amide. Regeneration of the carbonyl group can be achieved... 

The carbocation that is formed upon protonation of a carbonyl compound can lose H+ from the a-carbon to give an enol. Enols are good nucleophiles. Thus, under acidic conditions, carbonyl compounds are electrophilic at the carbonyl C and nucleophilic at the a-carbon and on oxygen, just like they are under basic conditions. Resonance-stabilized carbonyl compounds such as amides and esters are much less prone to enolize under acidic conditions than less stable carbonyl compounds such as ketones, aldehydes, and acyl chlorides in fact, esters and amides rarely undergo reactions at the a-carbon under acidic conditions. 

Pinacol formation from carbonyl compounds promoted by Smij continues to interest chemists. In the presence of methyl chloroformate the products are cyclic carbonates. In a cyclitol synthesis the diastereoselectivity for cyclization is found to be dependent on the a-substituents of the aldehyde groups. Lithium halides (chloride, bromide) have a profound effect on the reactivity of Sml2 and the pinacol coupling is favored. The reduction and pinacol coupling of ketones in THF is accelerated by MejSiCl (reaction time from hours reduced to a few minutes)." ... 

In the recent literature numerous reactions in which enamines are used for synthesis of enantiomerically pure compounds (EPC) can be found . Optically active enamines from substituted pyrrolidine (e.g. 27, R = CH20Me, CH20SiMe3, or 28, R = Me, CH20Me), or from piperidine , such as 29, (S)-phenylethylamine (30) " and stanna-N,0-heterocyclic amine (31) , are used. The cyclohexanenamines seem to be the preferred test compounds for this kind of reaction, whereas enamines of open-chain ketones and aldehydes have been investigated only rarely . Enamines from carbonyl compounds and secondary amines are obtained with azeotropic removal of water or by die Weingarten method with TiC. A titanium chloride-catalysed variation in which perfluorinated alkyl groups can be introduced is also known " . 

According to von Braun,125 Curtius degradation of a>bromo carboxylic acids provides a practical synthesis of aldehydes or ketones containing one fewer carbon atoms. The reaction from the a>bromo carbonyl chloride runs through the following steps ... 

Th. Harnitz-Harnitzky by the action of carbonyl chloride on aldehyde obtained what he called chloracetene, the composition and vapour density of which gave the formula C H Cl the chemical properties differed from those of monochlorethylene (vinyl chloride), discovered by Regnault. Chloracetene, which was also prepared by other chemists, was assumed to be CHg CCl, containing an unsaturated carbon atom. Kekule, who regarded such a compound as improbable, showed, with T. Zincke, that the supposed chloracetene is a mixture of aldehyde, paraldehyde, and carbonyl chloride. 

The laboratory synthesis of amino acids is fundamentally different from the way these compounds are synthesized in the living organisms (biosynthesis). The traditional synthesis of amino acids is known as Strecker synthesis (in the honor of Adolph Strecker). This method is based on the nucleophilic attack on the carbonyl group a reaction which we already discussed in this book. In this reaction of aldehyde with ammonium chloride and sodium cyanide the product is aminonitrile. By boiling with strong acid, this aminonitrile is transformed into the corresponding amino acid. 

Peterson Alkenation. Trimethylsilylmethyllithium (1) provides an alternative to a Wittig approach for the preparation of methylene compounds from carbonyl precursors. In some cases the use of (1) is superior to the Wittig approach. Condensation of (1) with a carbonyl compound results in the formation of a 8-hydroxysilane. Elimination to the alkene can be acconqtlished by use of acidic or basic conditions (eq 1). acetyl chloride or thionyl chloride can also be used to accomplish this elimination. A wide variety of aldehydes and ketones have been used as substrates in this reaction. The use of cerium(III) chloride has been advocated with reagent (1) to favor nucleophilic addition with enolizable carbonyl corrqtounds. The use of the lithium agent (1) gives superior yields compared to the use of trimethylsilylmethyl-magnesium chloride with cerium, ... 

A new synthesis of aldehydes with 2-methyl-2-thiazoline has the advantage of releasing the aldehydes from the thiazolidine intermediate under neutral conditions . Acetylene derivatives can be obtained from aldehydes via dibromomethylene compounds Novel reactions of alkynes with cationoid electrophiles have been published. -Diketones and 2-ketoalkoximes can be obtained by this reaction from acid chlorides and aliphatic nitro compounds respectively Addition of aldehydes to activated carbon-carbon double bonds occurs smoothly in the presence of cyanide ions as catalysts . Poly- -carbonyl compounds have been prepared by condensation of two anions, whereby the enolate salt of a y8-keto ester condenses as an electrophilic anion with strong nucleophiles such as the dianion of benzoylacetone. ... 

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