Carbonyl compounds Acyl chlorides Aldehydes

Many compounds contain more than one functional group Prostaglandin Ei a hormone that regulates the relaxation of smooth muscles con tains two different kinds of carbonyl groups Classify each one (aldehyde ketone carboxylic acid ester amide acyl chloride or acid anhydride) Identify the most acidic proton in prostaglandin Ei and use Table 1 7 to estimate its pK ... 

The chemistry of the carbonyl group is probably the single most important aspect of organic chemical reactivity Classes of compounds that contain the carbonyl group include many derived from carboxylic acids (acyl chlorides acid anhydrides esters and amides) as well as the two related classes discussed m this chapter aldehydes and ketones... 

Synthetic routes to a-ketol through the reactions of an unmasked acyl anion with carbonyl compounds are not numerous. The first practical application of an acylzirconocene chloride as an unmasked acyl anion donor was reported in the reaction with aldehydes in 1998 (Scheme 5.12 and Table 5.1) [19]. 

Dehalogenation.1 DMBI effects dehalogenation of a-halo carbonyl compounds in a variety of ethereal solvents with formation of DMBI+X in generally high yield. The order of relative reactivity is Br > Cl > F (halides) and primary > secondary > tertiary (for the a-substituted position). In combination with HO Ac (1 equiv.) the reagent also reduces acyl chlorides to aldehydes (70-90% yield). 

Another important part of Organic 11 is carbonyl chemistry. We look at the basics of the carbonyls in Chapter 9. It s like a family reunion where 1 (John, one of your authors) grew up in North Carolina — everybody is related. You meet aldehydes, ketones, carboxylic acids, acyl chlorides, esters, cimides, and on and on. It s a quick peek, because later we go back and examine many of these in detail. For example, in Chapter 10 you study aldehydes and ketones, along with some of the amines, while in Chapter 11 we introduce you to other carbonyl compounds, enols and enolates, along with nitroalkanes and nitriles. 

A. Medici, G. Fantin, M. Fogagnolo, and A. Dondoni, Reactions of 2-(trimethylsilyl)thiazole with acyl chlorides and aldehydes. Synthesis of new thiazol-2-yl derivatives, Tetrahedron Lett. 24 2901 (1983) A. Dondoni, G. Fantin, M. Fogagnolo, A. Medici, and P. Pedrini, Synthesis of (trimethylsilyl)thiazoles and reactions with carbonyl compounds. Selectivity aspects and synthetic utility, J. Org. Chem. 53 1748 (1988). 

Catalytic hydrogenation is often chosen as a method for reduction because of its chemoselectivity for C=C double bonds and benzylic C-X bonds over C=0 groups. The most important hydrogenation involving a carbonyl compound is not actually a reduction of the 0=0 double bond. Hydrogenation of acyl chlorides gives aldehydes in a 0 H2f Pd/BaS04... 

This is a good way of reducing compounds at the carboxylic acid oxidation level to aldehydes, which is why we included it in the table of carbonyl reductions on p. 622. The tertiary amine is needed both to neutralize the HCl produced in the reaction and to moderate the activity of the catalyst (and prevent over reduction). You will notice too that the catalyst support is different Pd/BaS04 rather than Pd/C. BaS04 (and CaCOs) are commonly used as supports with more easily reduced substrates because they allow the products to escape from the catalyst more rapidly and prevent overreduction. Acyl chlorides are among the easiest of all compounds to hydrogenate—look at this example. 

The most widespread use of IMPs is in the aza-Wittig reaction. This is the reaction of an IMP with a carbonyl group to generate an imine, or derivative thereof, with concomitant formation of the corresponding phosphine oxide (Scheme 2). The reaction is successful with a wide range of carbonyl containing compounds such as aldehydes, ketones, acyl chlorides, amides, and in some cases esters.2 Exposure to carbon dioxide, carbon disulfide, isocyanates, isothiocyanates, and... 

The a-halogenation reaction of carbonyl compounds was mentioned in Section 14-2. A different halogenation reaction is possible in which aldehydes can be directly converted to acyl chlorides by treatment with chlorine, but the reaction operates only when the aldehyde does not contain an a hydrogen and even then it is not very useful. When there is an a hydrogen, a halogenation (14-2, 12-4) occurs instead. Other sources of chlorine have also been used, among them SO2CI2 and f-BOCl. The mechanisms are probably of the free-radical type. A-Bromosuccinimide, with AIBN (p. 935) as a catalyst, has been used to convert aldehydes to acyl bromides. 

Acid-catalyzed addition of aliphatic, aromatic or heteroaromatic cyanohydrins to ethyl vinyl ether, n-butyl vinyl ether or dihydro-4//-pyran provides base stable, protected cyanohydrin derivatives. Phase transfer catalyzed alkylation of aliphatic cyanohydrins with allylic bromides gave a-substituted a-allyl-oxyacetonitrile. Carbonyl compounds react wiA cyanide under phase transfer catalysis to give cyanohydrin anions, which are trapped by an acyl chloride or ethyl chloroformate to give acyl- or alkoxycarbonyl-protected cyanohydrins respectively. The reduction of the carbonyl group of an acyl cyanide by NaBH4 under phase transfer conditions followed by esterification serves as an alternative route to aldehyde-derived cyanohydrin esters. ... 

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. 

Mg-promoted Reductive Cross-coupling of a,) -unsaturated Carbonyl Compounds with Aldehydes or Acyl Chlorides... 

Acyloxaziridines are easily obtained from compounds unsubstituted at nitrogen by reaction with acid chlorides or isocyanates. Acylation proceeds so smoothly that, in the amination of carbonyl compounds, oxaziridine compounds are obtained in better yields on addition of acid chlorides than in the absence of the acylating agent. With aliphatic aldehydes, amination does not succeed at all except in the presence of benzoyl chloride. Proof of structure comes from reduction by iodide to give the acid amide and carbonyl compound. 

---