Detection dicarbonyl compounds

In azo couplings with carbonyl compounds, three tautomeric products are possible, compared with only two for phenols and aromatic amines (discussed in Section 12.1). The ketohydrazone 12.75 is most often dominant, but for easily enolizable 1,3-dicarbonyl compounds (X=CO-R and similar structures) the azoenol 12.76 is the major product. The azoketone 12.77 is often postulated as primary product, but has rarely been identified in an unambiguous fashion using modern methods. The CH2 group should be easily detectable in the lH NMR spectrum. 

The pyrazole library was created sequentially using 10 mM solutions of the 1,3-dicarbonyl compound and 0.8 M solutions of the hydrazines, each introduced as a 2.5 pi slug [20]. This requires control of feeding of both reactant solutions so that the slugs enter the chip at the same time and mix thereafter. The residence time was 210 s. Thereafter, the reaction slugs were diluted on-chip by a 1 1 methanol-water stream at 8 pi min and detected. Analysis of the nature of the products and the degree of conversion was done using standards of reactant and product materials. 

With respect to the mechanism of the iron catalysis, the activity of FeCl3 -6H20 is closely related to its ability to give dionato chelate complexes 3 with [i-dicarbonyl compounds. Without prior deprotonation - even in Bronsted acidic media - these deeply colored iron complexes are instantly formed. With this property, Fe(III) is unique among all other transition metals, which require a stoichiometric amount of base for dionato complex formation. Known for over 100 years, the significant color of the complexes has been utilized for the detection of [i-oxo esters and [i-di ketones. 

M. A. Glomb and R. Tschimich, Detection of a-dicarbonyl compounds in Maillard reaction systems and in vivo, J. Agric. Food Chem., 2001, 49, 5543-5550. 

Another potential side reaction of the enediol(ate) intermediate is formation of the dicarbonyl compound, l-deoxy-D-glycero-2,3-pentodiulose 5-phosphate, resulting from p-elimination of the Cl-phosphate due to improper stabilization and/or premature dissociation of enediol(ate) from the enzyme active site. This compound has been characterized by reduction with borohydride, oxidation with H2O2, complexation with o-phenylenediamine, and 13C-NMR (23, 34). The p-elimination product is not detected in reactions with wild-type R. rubrum Rubisco but is formed in substantial amounts with mutants in which the Cl-phosphate ligands are substituted, demonstrating the required role of these amino acid side chains in stabilizing the enediol(ate) intermediate (34-35). 

In the case of 1,3-dicarbonyl compounds, the solvent frequently interferes with the coupling reaction. So with diethyl sodio malonate in ethanol [212b], methanol [212b], dimethylacetamide [212b], or HMPTA [216], besides the dimer and the trimer, the compounds LIXa-c are obtained. They are presumably formed by oxidation of the solvent to the aldehyde and its condensation with the active methylene compound. No dimer was detected in the oxidation of sodio acetoacetate in ethanol, with the major product being LX [217]. Anodic oxidation of cyclic 1,3-diketones in aqueous methanolic sodium hydroxide does not yield the dimer but product LXI, formed by condensation of the starting compound with formaldehyde [218]. 

Attempts to produce the analogous carbon-lead compounds by reaction of silyl enol et p-dicarbonyl compounds with aryllead triacetates under similar conditions were unsuccessf only products which were detected were the a-arylated P-dicarbonyl derivatives. 

Polymer 149, prepared by ring-opening polymerization (ROMP) of the corresponding functionalized norbornene, provides a clear illustration of the potential of this kind of materials. This resin catalyzes (12% molar) the reaction of linear aliphatic aldehydes with unsaturated ketones to provide 1,4-dicarbonyl compounds (153, Scheme 10.23) and was used for four consecutive cycles without any detectable decrease in performance [358]. A similar dimethylthiazolium structure supported on 2% cross-linked PS-DVB (150) was studied as catalyst for the acyloin condensation of a large variety of aldehydes [364], Catalyst 150 is used in 10 mol.% and the reaction takes place in ethanol at room temperature, with triethylamine as the base, to afford the corresponding a-hydroxyketones in excellent yields. Remarkably, the catalyst can be reused 20 times without losing its activity. 

Two points may be noted about the epimerization during the conversion of the 2-keto-n-glucoside into the 3-keto-n-glucoside, no 3-keto-n-mannoside was detected. Furthermore, no 2-keto-glycosides were found amongst the products from the 3-keto-n-glucoside. Small amounts of D-ribulose were also isolated from the 2-keto-D-glucoside at pH 7. The subsequent reactions of the dicarbonyl compound at pH 4 and 7 were, to a certain extent, different from those under alkaline conditions. 

Many types of reactive molecules are well known to medicinal chemists acyl halides, aldehydes, aliphatic esters, aliphatic ketones, alkyl halides, anhydrides, alpha-halocarbonyl compounds, aziridines, 1,2-dicarbonyl compounds, epoxides, halopyrimidines, heteroatom-heteroatom single bonds, imines, Michael acceptors and (l-heterosubstituted carbonyl compounds, perhalo ketones, phosphonate esters, thioesters, sulfonate esters, and sulfonyl halides, to name a few [14]. This is not to say that these functionalities are not useful - some even appear in approved drugs -but all of these can react covalently with proteins, and thus should be regarded with suspicion. However, molecules can react covalently with proteins even if they do not contain functionalities that raise alarm. Jonathan Baell has referred to these as pan assay interference compounds, or PAINS, and has published a list of moieties to watch out for, as well as strategies to detect them [15, 16]. 

Substituted cyclooctynes have been known to undergo autoxidation to diketone products probably via dioxetene type intermediates 69 [264]. The autoxidation of 1-phenylpropyne-l, 1-phenylbutyne-l and 1-phenyl-3-methyl- butyne-1 leads predominantly to benzoic anhydride, phenyl benzoate and benzil [265]. The corresponding a-dicarbonyl compounds have also been detected, which are intermediates in the oxidative cleavage of the triple bond. 

Like all a-dicarbonyl compounds, deoxyosones can be stabilized as quinoxalines by a trapping reaction with o-phenylenediamine (Formula 4.58) and subsequently quantitatively determined using liquid chromatographic techniques. In this way, deoxyosones were detected for the first time as intermediates in carbohydrate degradation. 

Thus, the complete lack of sensitivity to mutations and the failure of detecting any free long chain diketoacids in B-diketones containing waxes are against to the suggestion that B-dicarbonyl compounds arise via decarboxylation. 

In order to detect cis-enols of jS-dicarbonyl and a-dicarbonyl compounds, the formation of yellow-red, red to blue-violet, and blue colors with ferric chloride solution in absolute methanol is commonly used. Chelates of the following type are formed ... 

When acetylene is employed at atmospheric pressure (KOH/DMSO, 120°C, 5 h), deoximation of the dioxime and resinification processes, due to autocondensation of the dicarbonyl compounds under the action of KOH/DMSO system, become prevailing. In these cases, dipyrroles are detected in trace amounts only. 

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