Dicarbonyl compounds retrosynthetic analysis

Figure 17-1 presents atypical retrosynthetic analysis problem. (The presence of a p-diccirbonyl compound indicates that the formation of a carbanion through the loss of a hydrogen ion from the a-carbon will probably be important however, don t let this distract you from the task at hand.) The problem asks you to prepare a ketone. Your first question should be, How can 1 prepare a ketone One answer to this question is to deccirboxylate a 5-dicarbonyl compound. For the compound in this problem, the reaction shown in Figure 17-2 works. 

The preparation of (83) (Expt 8.29) is an example of the Hantzsch pyridine synthesis. This is a widely used general procedure since considerable structural variation in the aldehydic compound (aliphatic or aromatic) and in the 1,3-dicarbonyl component (fi-keto ester or /J-diketone) is possible, leading to the synthesis of a great range of pyridine derivatives. The precise mechanistic sequence of ring formation may depend on the reaction conditions employed. Thus if, as implied in the retrosynthetic analysis above, ethyl acetoacetate and the aldehyde are first allowed to react in the presence of a base catalyst (as in Expt 8.29), a bis-keto ester [e.g. (88)] is formed by successive Knoevenagel and Michael reactions (Section 5.11.6, p. 681). Cyclisation of this 1,5-dione with ammonia then gives the dihydropyridine derivative. Under different reaction conditions condensation between an aminocrotonic ester and an alkylidene acetoacetate may be involved. 

The retrosynthetic analysis of 2,4,6-triphenylpyrylium tetrafluoroborate (86), involving an initial reduction followed by a disconnection of one carbon-oxygen bond (cf. disconnection of 2,5-dimethylfuran, Section 8.3.1, p. 1146), reveals the substituted 1,5-dicarbonyl compound (89). Further rational disconnection then reveals acetophenone and l,3-diphenylprop-2-en-l-one (chalcone) clearly the latter may originate from acetophenone and benzaldehyde (cf. Section 6.12.2, p. 1032). 

Our retrosynthetic analysis of the Paal-Knorr synthesis leads to a problem when applied to furan, as it implies addition of a water molecule, followed by elimination of two water molecules. In practice, simple dehydration of a 1,4-dicarbonyl compound leads to furans as in the preparation of 2.21. 

Disconnection of the N1-C6 bond in generalised pyrimidine 10.11 in the usual way produces enol 10.12, which exists as ketone 10.13. Similarly, disconnection of the carbon-nitrogen double bond in 10.13 yields a dicarbonyl compound 10.14 and an amidine 10.15. This retrosynthetic analysis, suggesting the combination of bis-electrophilic and bis-nucleophilic components, is the basis of a very general pyrimidine synthesis. 

For retrosynthetic analysis (see Fig. 6.26) the 1,2,4-triazine system offers two favourable routes. Route a After cleavage of the N-4/C-5 bond via the intermediate 15, route a leads to 1,2-dicarbonyls and amidrazones or semicarbazides as possible building-blocks. Alternatively, NH3 elimination from 15 suggests 1,2-dicarbonyl compounds and hydrazides via the intermediate 17 as potential starting materials. 

Use retrosynthetic analysis to choose the appropriate p-dicarbonyl compound and alkyl halide to prepare each of the following ... 

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