1.3- dicarbonyl compounds derivatives

Unsymmetrical 1,3-dicarbonyl compound derivatives Unsymmetrical enaminones Conjugate Addition to Alkynes... 

The formation of an allenyl ketone as the sole product can be achieved by using an excess (2 equiv.) of propargyl bromide (entries 3—6, Table 5.9). Use of an increased amount (3 equiv.) of the acylzirconocene chloride in the reaction with propargyl bromide and/or tosylate yields a significant amount of a 1,4-dicarbonyl compound derived from Michael-type addition of the acylzirconocene chloride to the initially formed allenyl ketone (entry 2, Table 5.9). The Michael-type addition of acylzirconocene chlorides to allenyl ketones under Cu(I)-catalyzed conditions has been confirmed by an independent experiment (Scheme 5.31). 

The imidazole part of the IQ-compounds suggests creatinine as a common precursor. The remaining parts of the IQ-compounds could arise from Maillard reaction products, e.g., 2-methylpyri-dine or 2,5-dimethylpyrazine. These two compounds could be formed through Strecker degradation. In Maillard reactions, this is induced by a-dicarbonyl compounds derived from carbohydrates, which are thereby converted to pyrroles, pyridines, pyrazines, etc. (8). 

Magneron et al. (2003) determined products for the OH-initiated oxidation of 4-hydroxy-4-methyl-2-pentanone (diacetone alcohol). They obtained molar yields, in the presence of NO, of (94 14)% for acetone and (10 2)% for PAN and an unquantified yield of CH2O. They had indications of a dicarbonyl compound, derived from the parent structure, with the second carbonyl on the 3-position. Their carbon balance was about 53%, showing that there were many undetermined compounds. They proposed mechanisms for the formation of the observed products based on abstraction at the 1-, 3-, and 5-positions. 

Analysis Another lactone FGl reveals the true TM (A). Our normal discormection a of an a,p-unsaturated carbonyl compound gives us the 1,5-dicarbonyl compound (B) and the ketone (C) clearly derived from phenol. Alternatively we could disconnect bond b to the keto-ester (D) with the further discormection shown ... 

Cyclohexene derivatives can be oxidatively cleaved under mild conditions to give 1,6-dicarbonyl compounds. The synthetic importance of the Diels-Alder reaction described above originates to some extent from this fact, and therefore this oxidation reaction is discussed in this part of the book. 

Most of the reactions of ester enolates described so far have centered on stabilized eno lates derived from 1 3 dicarbonyl compounds such as diethyl malonate and ethyl ace toacetate Although the synthetic value of these and related stabilized enolates is clear chemists have long been interested m extending the usefulness of nonstabilized enolates derived from simple esters Consider the deprotonation of an ester as represented by the acid—base reaction... 

It is customary to perform the condensation of 1,4-dicarbonyl compounds with hydrazines in the presence of mineral acid to avoid the formation of A-aminopyrroles. Contrary to early claims that 4,5-dihydropyridazines are formed <07CB4598), these compounds are now regarded as 1,4-dihydro derivatives 81CB564). 

Another possibility is that both nitrogen atoms react with a double alkylating agent. In this way fused pyrazole derivatives (pyrazolo[l,2-a]pyrazoles) like (237) can be obtained by reaction of 3,5-dimethylpyrazole with 1,3-dichloropropane or l-chloro-3-propanol (69BSF2064). More surprising is the reaction with a-chlorocarbonylphenylketene which yields the paraionic compound (238) (80JA3971) which can also be obtained from 3,5-dihydroxy-4-phenylpyrazole and /3-dicarbonyl compounds (82JOC295). 

The carbonyl group forms a number of other very stable derivatives. They are less used as protective groups because of the greater difficulty involved in their removal. Such derivatives include cyanohydrins, hydrazones, imines, oximes, and semicarbazones. Enol ethers are used to protect one carbonyl group in a 1,2- or 1,3-dicarbonyl compound. 

The chloride of triflic acid (trifluoromethanesulfonyl chloride) is an effective sulfonylating agent Like triflic anhydride, it usually reacts with alcohols and other nucleophiles with the formation of the corresponding derivatives of tnflic acid [69] However, in some reactions, it acts as a chlorinating reagent [98] The reactions of tnfluoromethanesulfonyl chloride with 1,3-dicarbonyl compounds or some carboxylic esters in the presence of a base result m the formation of chlonnated products in high yields (equation 49)... 

The formation of vinylogous amides from primary amines and -dicarbonyl compounds gives rise to hydrolyzable amine derivatives with greatly decreased nucleophilicity of the nitrogen function. Thus these derivatives have found some use as protecting groups in peptide syntheses 617-619). 

The wide applicability of the PK reaction is apparent in the synthesis of pyrroles, for example, 45, en route to novel chiral guanidine bases, levuglandin-derived pyrrole 46, lipoxygenase inhibitor precursors such as 47, pyrrole-containing zirconium complexesand iV-aminopyrroles 48 from 1,4-dicarbonyl compounds and hydrazine derivatives. The latter study also utilized Yb(OTf)3 and acetic acid as pyrrole-forming catalysts, in addition to pyridinium p-toluenesulfonate (PPTS). 

Subsequent to Hantzsch s communication for the construction of pyridine derivatives, a number of other groups have reported their efforts towards the synthesis of the pyridine heterocyclic framework. Initially, the protocol was modified by Beyer and later by Knoevenagel to allow preparation of unsymmetrical 1,4-dihydropyridines by condensation of an alkylidene or arylidene P-dicarbonyl compound with a P-amino-a,P-unsaturated carbonyl compound. Following these initial reports, additional modifications were communicated and since these other methods fall under the condensation approach, they will be presented as variations, although each of them has attained the status of named reaction . 

The condensation of 1,3-dicarbonyl compounds 1 with amidines 2 catalyzed by acids or bases to give pyrimidine derivatives 3 is regarded as the Pinner pyrimidine synthesis. ... 

Many pyrimidine derivatives have been prepared via the Pinner procedure. Amidines react with 1,3-dicarbonyl compounds to form 2, 4, 6-trisubstituted pyrimidines. ... 

Monoamino derivatives react with (3-dicarbonyl compounds in a different way. Thus, the synthesis of an unusual fused pyrimidine 190 has been achieved via condensation of 4-amino-3-phenylfuroxan with acetylacetone in the presence of... 

Ultraviolet and infrared spectroscopy indicate that quinoxaline-2,3-dione type structures are preferred to tlie tautomeric 3-hydroxy-quinoxalin-2 One or 2,3-dihydroxyquinoxaline forms. The light absorption properties (UV) of quinoxaline-2,3-dione have been compared with those of its NN -, ON-, and OO -dimethyl derivatives (79, 80, and 81), and also its N- and 0-monomethyl derivatives (43 and 82). The parent dicarbonyl compound and its mono- and di-A -methyl derivatives show very strong carbonyl absorption near to 1690 cm split into two peaks. 

Hydrogens on carbon next to a carbonyl group are acidic. In general, a /3-dicarbonyl 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. 

The best Michael reactions are those that take place when a particularly stable enolate ion such as that derived from a /i-keto ester or other 1,3-dicarbonyl compound adds to an unhindered a,/3-unsaturated ketone. Tor example, ethyl acetoacetate reacts with 3-buten-2-one in the presence of sodium ethoxide to yield the conjugate addition product. 

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