Chromones, from phenols

Although there is evidence that chromone syntheses which proceed by the cyclization of phenyl esters under Friedel-Crafts conditions may involve a Fries rearrangement and hence require the formation of one bond adjacent to the heteroatom, syntheses of chromones from phenols will be considered together in this section. The Simonis reaction (530R(7)l)... 

Simonis chromone cyclization. Formation of chromones from phenol and (3-keto esters in the presence of phosphorus pentoxide, phosphorus oxychloride, or sulfuric acid. Coumarins may also be formed. 

Chromones from phenols and p-ketoesters using phosphorus pentoxide. 

Whilst the majority of chromone syntheses from phenols involve cyclization y to the heteroatom and are discussed later, there are some instances where ring closure occurs at the heteroatom. For instance, 1,3-dimethoxybenzene is acylated by 2,3,3-trichloropropenoyl chloride in the presence of aluminum chloride to give 2,3-dichloro-7-methoxychromone (64CB80). 

For several years our respective groups have investigated the formation of aromatic compounds from carbohydrates in aqueous solution at various pH-values under reflux or hydrothermolytic conditions. For instance, previous papers(1-6) in this series concerned the degradation of hexoses, pentoses, erythrose, dihydroxyacetone, and hexuronic acids to phenolic and enolic components. Of particular interest were the isolation and identification of catechols, an acetophenone, and chromones from pentoses and hexuronic acids at pH 4.5 (1,2). The formation of these compounds, as well as reductic acid(7),was found to be more pronounced than that of 2-furaldehyde(2) under acidic conditions. 

One of the few nonnitrogenous compounds to show spasmolytic activity is a rather simple chromone. Acylation of the phenolic ketone, 31, with the half ester-half acid chloride from oxalic... 

Dicoumarol Dicoumarol, 3,3 -methylene-bis(4-hydroxycoumarin) (24.1.8), is synthesized from 4-hydroxycoumarine (24.1.7), which is in turn synthesized from salicylic acid methyl ester by cyclization to a chromone derivative using sodium or sodium methoxide or from o-oxyacetophenone by reacting it with diethylcarbonate in the presence of sodium ethoxide. Condensation of the resulting 4-hydroxycoumarin with formaldehyde as a phenol component gives dicoumarol [6-9],... 

Syntheses of 2- and 3-substituted chromones normally start from 2-hydroxyphenyl ketones. In the first of two examples, a route to flavone is shown in Scheme 5,10 using 2-hydroxyacetophenone (2-hydrox-yphenylethanone) and benzoyl chloride as starting materials. Initially, the phenolic group of the acetophenone is O-acylated by benzoyl chloride, using pyridine as a base (a Schotten-Baumann-type reaction). 

However, chromones react differently, because the phenolic hydroxy group in the ring-opened intermediate is unreactive. Thus, isoxazoles (264) result from the reaction with hydroxylamine, and a pyrazole is formed with hydrazine. y-Pyrones also give pyrazoles with hydrazine. 

Aloe is a medicinal plant that has been used since ancient times by cultures in many countries and continents for many of the same applications. Africa is blessed with a wide variety of Aloe spp. each used by the indigenous cultures. Fleshy leaves are the source of two of the main products, gel and latex, with both products showing distinct differences in their chemical composition. Chemical composition of gel consists mainly of water with carbohydrate polymers and a range of other organic and inorganic components. In contrast, the chemical composition of the latex includes many phenolic compounds such as anthraquinones and chromones. The objective of this paper is to review the the botany, chemistiy and pharmacological properties of Aloes from Africa. 

The concept utilised was based on a retrosynthetic analysis comprising a nicotinic acid derivative (41) and a dihydroxychromone. The nicotinic acid moiety was prepared by lithiation of nicotinaldehyde followed by treatment with trimethyltin chloride. After benzoylation of the chromone noreugenin to protect the free phenolic group the compound was brominated to yield (42) and the two compounds formed were reacted with the nicotinic derivative to give a C-C bond with either the 6 or 8 of the chromone to give a compound such as (43) from which isoschumanniophytine or schumanniophytine respectively could be easily obtained by debenzoylation and lactonisation. 

The comparison of these with the charge distribution on chromones and napththoquinones revealed the gradual shift from the phenol- to the urea-type inhibitors. 

Fluoroalkyl chromone derivatives can be obtained from the base catalysed reaetion between 2,2-dihydropolyfluoroalkanoates and phenols. Initial loss of HF allows Michael addition of the phenol and subsequent cyclisation of the enol ether yields the heterocycle. m-Substituted phenols give the expected mixture of 5- and 7-substituted chromones, whilst dihydroxy aromatic compounds give polycyclic materials (94JFC263). In a more conventional approach Z-3-(aryloxy)-polyfluoroalkenoic adds, derived from Michael addition of phenols to polyfluoro-2-alkynoic acids, undergo intramolecular Friedel-Crafts acylation to 2-polyfluoro-alkylchromones (94JFC25). 

Chemo- and regioselective synthesis of naphtho[2,3-c]chromenes result from the palladium-catalyzed reaction of 2-haloaryl aUenes with 2-alkynyl-phenols in refluxing 1,4-dioxane (Scheme 18) (14CC5891). Another palladium catalyst was involved in the intramolecular oxidative cyclization of 3-allyl-2 -hydroxyflavones to afford chromone[2,3-c]-2f/-chromenes in good... 

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