Chromones 4- chromanones

Another problem for the synthetic use of PFR is that the ortho-rearranged products may act as internal light filters, stopping the reaction. In synthetic routes leading to chromanones, chromones, and related compounds, this is of vital importance because the overall yield is limited by the photochemical step. Improved yields can be obtained if the a, 3-unsamrated orr/io-hydroxyphenones resulting from PFR are removed and cyclized to chromanones. This can be acomplished in one pot by irradiation in a two-phase system benzene/10% aqueous NaOH, whereby chromanones are directly obtained from phenyl crotonates in 80-90% yields [210]. 

The scarcity of reviews1 and recent interest in thiochromanones and related compounds calls for a comprehensive summary of this area of heterocyclic chemistry. The apparent similarity between these systems and the naturally occurring chromanones, chromones (flavones), chromenes, etc., is responsible for the continued importance of these sulfur heterocycles. Chemical Abstracts (through November, 1973) has been employed as the principal reference source and nomenclature guide for this review. 

Coumarins and isocoumarins appear to be of varied origins. Simple coumarins, such as umbelliferone, are formed by the shikimic acid pathway in which hydroxylation of p-hydroxycinnamic acid occurs. Other coumarins, for example alternariol (690), are derived from a polyketide unit, as are a number of chromanones, chromones, pyranones and isocoumarins (B-78MI22400). The biosynthesis of 5-hydroxy-2-methylchromone has been shown to involve the chromanone (60JCS654). However, isocoumarins are also derived from the mixed acetate-shikimate route, through initial cyclization of the polyketide and subsequent lactonization. 

The effect of concentration, temperature, and solvent on the photodegradation of benzothiazolinospiropyrans using flash photolysis has been presented. trans-Cyclo-octene is shown to be the major product in the photolysis of m-cyclo-octene with a quantum yield of 0.34. Hamanoue and co-workers " report on intersystem crossing and lowest triplet states of 4-chromanone, chromone, and flavone and of some nitroanthracene derivatives." For the latter long build-up times for triplet-triplet absorption were observed (72—86 psec) and represent the effect of the rates of internal conversion T aa/ T,). Indirect intersystem crossing to higher levels of the triplet manifold is most important in these systems. 

R] (a) Hauser, C. R. Swamer, F. W. Adams, J. T. Org. React. 1954, 8, 59. [R] (b) Ellis, G. P., Chromenes, Chromanones, and Chromones from The Chemistry of Hetereocylic Compounds, Weissberger, A. and Taylor, E. C., eds John Wiley Sons, 1977, vol. 31, New York, p.495. Note The author in the former reference refers to the formation of chromones, coumarins, and flavones as the Kostanecki acylation while the latter author calls the formation of chromones and coumarins the Kostanecki-Robinson reaction. 

It is known that tropylium may be prepared from tropylidene via hydride abstraction by PhgC or MegC carbonium ions therefore, it is very likely that here too the dehydrogenation is a hydride transfer from the 1,5-dione to an acceptor. A similar dehydrogenation of chromanones to chromones, with triphenylmethyl perchlorate was reported. A study of the electrooxidation of 1,5-diones on a rotating platinum electrode showed that 1,5-diaryl-substituted diones afford pyrylium salts in these conditions and that the half-wave potentials correlate with yields in chemical dehydrogenations. 

Phenols are also suitable nucleophiles for 5-alkylidene-l,3-dioxane-4,6-diones, when activated by Yb(OTf)3. Depending on the substitution pattern at C-1, several useful coumarins, dihydrocoumarins, 4-chromanones, and chromones were obtained (Scheme 21) <2006JOC409>. 

In principle, the relative configuration in these and related cases can be identified by spectroscopic analysis, however, in practice this is not always simple to achieve. For example, the conjugate addition of a methyl group to the racemic chromone rac-9 could generate four pairs of diastereomeric chromanones (rac-10-rac-13). In the event, two main products in a 4 1 ratio were obtained. The relative configuration was not clear from the H-NMR coupling constants (J2,3) and was, therefore, determined by chemical reactions108 (see pp 472 and 480). 

A number of 2,3-fused chromones have been prepared from ethyl chloroformate and acetylsalicylic acid, a source of the mixed anhydride of formic and salicylic acids, and piperidinocycloalkenes (69JCS(C)935). A plausible mechanism is outlined in Scheme 165. It has not proved possible to isolate the chromanone (460) but the formation of 3-acetyl-2-methylchromone from 2-pyrrolidinopropene lends support to the intermediacy of the chromanone. The migration of the acyl group from oxygen to carbon is supported by the synthesis of 3-benzoyl-2-methylchromone rather than 3-acetylflavone from benzoylsalicylic acid and the pyrrolidinopropene. 

The direct conversion of a chromanone to a chromone by dehydrogenation has been achieved using palladium on charcoal <74CR(C)(279)l5l> and with selenium dioxide (65JCS2743), but both reagents appear to be somewhat fickle. 

Similarly, chromanones are converted into benzopyrylium salts in this case though the oxidant is triphenylmethyl perchlorate. Hydrolysis affords the chromone (60CB1466, 60CI(L)1192>. 

Chromones of therapeutic interest have been reviewed (70FES57) and the pharmacological activity associated with chromanones has been discussed (77HC(3l)345>. 

Flavonoids are more or less intensely yellow colored pigments belonging either to the group of 2-phenyl-chromones 39 (flavones, flavonols) or 2-phenyl-chromanones 391 (flavanones, flavanonols) both groups have a backbone of 2-phenyl-l,4-benzopyrones ... 

The cycloaddition of ketene acetals to 3-formylchromone exhibits good diastereoselectivity and meihanolysis of the pyrano[4,3- ] -pyran affords the chromanone ester (21) without racemisation. The chiral auxiliary, the diol (22), can be recyclised and the overall process represents an asymmetric conjugate addition to the chromone (95 JCS(P1 )2293). 

Ketones derived from pyrans are called pyranones (also commonly pyrones), and the parent compounds are pyran-2-one 17 and pyran-4-one 18. Trivial names are used for the related benzo analogs coumarin 19, isocoumarin 20, dihydrocoumarin 21, chromone 22, xanthone 23, and chromanone 24. 

The reduction of substituted chromones 402 with 9-borabicyclo[3.3.1]nonane (9-BBN) proceeds in a regioselective fashion to give 2/7-chromenes 403 (Scheme 66). Other boranes resulted in reduction to give chromanones <2001BCJ967>. 

Chemistry of Heterocyclic Compounds 1977 , Volume 31 (Chromenes, Chromanones, and Chromones). 

G. P. Ellis, Chromenes, Chromanones and Chromones, Wiley (Interscience), New York, 1977. 

Diazochromanone (65) undergos rapid elimination of the diazo group in the presence of BF3-Et20 to furnish chromone (232). 4 This method is complementary to procedures that are reported for the transformation of appropriately substituted chromanone to chromone. 

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