Dicarbonyi compound

One of the most common approaches to pyrazine ring construction is the condensation of diaminoethane and 1,2-dicarbonyI compounds such as 206 to provide pyrazines 207 after aromatization. Aromatization was accomplished by treating the dihydropyrazines with manganese dioxide in the presence of potassium hydroxide <00JCS(P1)381>. The N-protected 1,2-dicarbonyl compounds 206 were prepared from L-amino acids by initial conversion into diazoketones followed by oxidation to the glyoxal. 

Oxidation of aldehyde or ketones to 1,2-dicarbonyi compounds with Se02 (sometimes oxidation to a.p-unsaturated ketones). 

Reconnection can also be used in the synthesis of 1,2-dicarbonyi compounds since oxonolysis of enones (11) gives a-keto aldehydes (12) or acids (13) depending on the work-up. Ozonolysis of enones of type (14) gives a diketones. 

Some other methods to synthesize 1,4-dicarbonyI compounds via cyclopropane or cyclobutanone derivatives are given in sections 1.13.1 and 1.13.2. 

Both the malonic ester synthesis and the acetoacetic ester synthesis are easy to cany out because they involve unusually acidic dicarbonyi compounds. As a result, relatively mild bases such as sodium ethoxide in ethanol as solvent can be used to prepare the necessary enolate ions. Alternatively, however, it s also possible in many cases to directly alkylate the a position of monocarbonyl compounds. A strong, stericaliy hindered base such as LDA is needed so that complete conversion to the enolate ion takes place rather than a nucleophilic addition, and a nonprotic solvent must be used. 

Enamines behave in much the same way as enolate ions and enter into many of the same kinds of reactions. In the Stork reaction, for example, an enamine adds to an aqQ-unsaturated carbonyl acceptor in a Michael-like process. The initial product is then hydrolyzed by aqueous acid (Section 19.8) to yield a 1,5-dicarbonyi compound. The overall reaction is thus a three-step sequence of (11 enamine formation from a ketone, (2) Michael addition to an a,j3-unsaturated carbonyl compound, and (3) enamine hydrolysis back to a ketone. 

Three synthetic approaches for benzopyrones have been developed that use Gly as starting material. Hippuric acid was transformed with acetic anhydride into 2-phenyl-5(4//)oxazolone or further into its 4-ethoxy-methylene derivative, then reacted with cyclic 1,3-dicarbonyI compounds (such as like dimedone) to form 100 [90LA501 92H(33)843]. On the other hand, when hippuric acid was transformed into methyl 2-benzoyl-amino-3-dimethylaminopropenoate, it reacted with resorcinol to give a 7-hydroxybenzopyrone derivative (89JHC1273). 

In 1,3-dicarbonyI compounds such as acetylace-tone, the protons between the two carbonyls will be even more acidic (p Ta 9), since there are now two carbonyl groups exerting their combined influence. It can also be seen that resonance in the enolate anion is even more favourable with two carbonyl... 

Anodic oxidation of catechols enables the unstable quinones to be prepared and reacted in situ. Reaction of the 1,2-quinone with a 1,3-dicarbonyi compound gives a high yield of a benzofuran [123, 124]. Both 1,2- and 1,4-quinones, prepared electrochemically in nitromethane, are efficiently topped in Diels-Alder reactions with butadienes [125]. 

Hydrogens on carbon ne.xt to a carbonyl group are acidic. In general, a jS-dicarbonyi compound is most acidic, a ketone or aldehyde is next most acidic, and a carboxylic acid derivative is least acidic. Remember that alcohols, phenols, and carboxylic acids are also acidic because of their -OH hydrogens. 

Dicarbonyi compound (Section 23.2) A compound containing two carbonyl groups separated by a single carbon atom. 

In contrast to simple carbonyl compounds, 1,3-dicarbonyI compounds—like acetoacetic ester or 2,4-pentanedione (acetylacetone)—exist to an appreciable extent in the enol form. 

Standard heterocyclic syntheses tend to have a name associated with them and it is simply not worth while learning these names. Few chemists use any but the most famous of them we will mention the Knorr pyrrole synthesis, the Hantzsch pyridine synthesis, and the Fischer and Reissert indoie syntheses. We did not mention that the synthesis of furans from 1,4-dicarbonyi compounds is known as the Feist-Benary synthesis, and there are many more like this, if you are really interested in these other names we suggest you consult a specialist book on heterocyclic chemistry. 

When a hydr< en atom is flanked by two carbonyl groups, its aodif is enhanced even more. Table 22.1 thus shows that compounds such as diketones (/l diketones), 3-oxo esters (p-keto esters), and 1,3-diesters are more acidic than water. This enhanced acidity of /3-dicarbonyI compounds is due to the fact that the resultant enolate ions are stabilized by delocalization of the negative charge over two carbonyl groups. Hie enolate ion of 2,4-pentanedione, for example, has three resonance forms. Similar resonance forms can be drawn for other doubly stabilized enolate ions. 

Synthesis of 1,3-dicarbonyi compounds by this approach requires the acylation of malonates or other simple 1,3-dicarbonyl compounds as a first step. Sodium or potassium enolates (58) acylate on oxygen but in the corresponding magnesium enolates (59) the oxygen atoms are chelated by the metal, leaving the carbon free to react. 

Tliere is no reason why 1,6-difunctionahsed compounds should not be made by conventionat methods, essentiaHy ignoring the 1,6-rciationship. The symmetrical spiro ketone (2S) disconnects to 1,6-dicarbonyi compound (29) which conid no doubt be made by cleavage of (30), An alternative approach is to disconnect the ring from the chain to give (31) easily made from butyro-lactone (32) (Table 25.1). 

Both target molecules (19) and (21) disconnect to the same 1,6-dicarbonyi compound (20) and reconnection gives the naturally occurring limonene (22) whose synthesis we discussed in Chapter 17. 

The simplest disconnection of furans U) or pyrroles (9) is the removal of the heteroafom leadng a 1,4-dicarbonyi compound < ) to be made by the methods of Chapter 25,... 

In Section 23-2 two reactions of /3-tlicarbonyl compoiiiiJs arc presented. The (irst is alkylation of the readily deprotonated "carbon in the middle." The second pertains to /3-dicarbonyi compounds where at least one of the carbonyl groups is an ester. Ester hydrolysis leads to a carboxylic acid that readily loses COi (decarboxylation). When this sequence is carried out on a /3-ketocster, the result is a ketone. When carried out on a diester of propanedioic (malonic) acid, the result is a carboxylic acid. In each case, groups attached in the preliminary alkylation slep(s) wind up in the product. 

Specific enoi equivaients from 1,3-dicarbonyi compounds... 

Conjugate additions with 1,3-dicarbonyi compounds were discussed in Chapter 25. if you have read Chapter 28 then you shouid be aware that such reactions are an exceiient way of making 1,5-difunctionaiized compounds. 

The Knoevenagel reaction of 2,3-O-isopropylidene-D-glyceraldehyde with active methylene compounds has led to derivatives of D-fructose and D-sorbose (Scheme 6). Similar condensations with other 3-dicarbonyI compounds led to furan derivatives on acidic hydrolysis. In the self-condensation of D-fructose... 

Halland N, Hansen T, Jprgensen KA (2003) Organocatalytic Asymmetric Michael Reaction of Cyclic 1,3-DicarbonyI Compounds and a,(3-Unsaturated Ketones - A Highly Atom-Economic Catalytic One-Step Formation of Optically Active Warfarin Anticoagulant. Angew Chem Int Ed 42 4955... 

MuH = electnori rich aromatics, p-dicarbonyi compounds, ketones, enalates, allyl silanes, hydride, amines, enamines [O] = FefNOs )3. Ce(NH4)2 (I Ogfe. (CHg h NO... 

Pyrazole synthesis from a p-dicarbonyi compound and a hydrazine (see 1st edition). 

When the product of a Michael reaction is also a P-keto ester, it can be hydrolyzed and decar-boxylated by heating in aqueous acid, as discussed in Section 23.9. This forms a 1,5-dicarbonyi compound. Figure 24.7 shows a Michael reaction that was a key step in the synthesis of estrone,... 

Figure 2.58 Strecker degradation of a-amino acids by a-dicarbonyi compounds.

Figure 4.55 Formation of acetic acid by cieavage of a- and p-dicarbonyi compounds.

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