Benzo chromones

Methyl-7.8.benzo cumarin-oxim 17 1195. 2 Metl l-5.6 benzo chromon-oxlm... 

Benzaldehyd> 4 azo 4) benzoes ine-athyleeter 16, 236. nLm -Azozyaoetbphenon 16, 643. p.p -Azoxyaoetopnenon 16, 643. 2-Methyl>3 acetyl-5.6>benzo Chromon dionm 17II502. 

Method B involves the preparation of precursor of 2-alkyl-l-benzo-pyrylium salts, as shown in Scheme ll.50 2-Alkylbenzopyrylium salts have been prepared by condensation of salicylaldehyde with appropriate ketone in acetic acid or by alkylation or reduction of coumarin or chromone derivatives. Reaction of 2-alkylbenzopyrylium salts with salicylaldehyde gives directly a spirodibenzopyran or 2-vinynologue benzopyrylium salt 17 which then can be converted into the spirodibenzopyran by piperidine or pyridine. 

In order to study any chemoselectivity influences of microwave irradiation on the domino Knoevenagel/hetero-Diels-Alder process (the so-called Tietze reaction), Raghunathan and coworkers [31a] investigated the transformation of 4-hydroxy coumarins (10-85) with benzaldehydes 10-86 in EtOH to afford pyrano[2,3-c]cou-marin 10-87 and pyrano[2,3-b]chromone derivatives 10-88. Normal heating of 10-85a and 10-86a at reflux for 4h gave a 68 32 mixture of 10-87a and 10-88 in 57% yield, whereas under microwave irradiation a 97 7 mixture in 82% yield was obtained. Similar results were found using the benzo-annulated substrates 10-85b and 10-86b. 

Pyran-4-one (56a) and its benzo derivative (chromone) show chemical properties in agreement with substantial jr-electron delocalization and consistent with a betaine structure 56b (Scheme 27). Experimental data have therefore generated numerous theoretical studies on the aromaticity of pyranones, which have been extensively reviewed.219 Earlier studies suggested that chemical shifts and coupling constants... 

In contrast to the benzoannelated nitrogen heterocycles, only a few kinds of benzoannelated systems without nitrogen have been described (Fig. 3.15). Five-mem-bered rings such as benzo[b]furans (336) [184, 461] and hydrobenzo[b]furans (337) (Scheme 3.41) [337, 462, 463] and six-membered rings like 4H-l-benzopyran-4-ones (4-chromones) (338) and 2H-l-benzopyran-2-ones (coumarines) (339) [96, 464, 465] 2,3-dihydro-4H-l-benzopyran-4-ones (chroman-4-ones) (340) [466] and 3,4-dihydro-lH-2-benzopyrans (isochromans) (341) [444] have been reported. 

Electrophilic aromatic substitution of other benzo-fused v-deficient systems generally follows predictable pathways. Thus, benzopyrylium salts are in general resistant to electrophilic substitution even in the benzo-fused ring. Chromones behave somewhat similarly, although substitution can be effected under forcing conditions. Coumarins, on the other hand, undergo nitration readily in the 6-position while bromination results in substitution at the 3-position as a consequence of addition-elimination. 

The basicity of pyran-4-one, which is significantly greater than that of simple aromatic and aliphatic ketones, is apparent from its pKa of 0.1 and has been rationalized in terms of a betaine structure (212 X = O). Benzo-fusion increases the basicity the p2sTaof chromone (20) is 2.0 (65ZOB1707). As a result of their basicity, both pyran-4-one and chromone have a great propensity to form salts with acids (63CJC505). 

Interest in the antibiotic bikaverin (531), a fungal metabolite with a benzo[Z>]xanthone skeleton, has culminated in its total synthesis (76JCS(Pl)499). The chromone moiety (530) was constructed as shown and the xanthone was obtained by cyclization of the acid chloride (Scheme 196). 

Photodimerizations have been observed in a variety of sulfur-containing heterocycles notable examples include the photodimerization of 2- and 3-ary lbenzo[b]thiophens,287 benzo[h]thiophen 1-oxide,288 benzo[h]thiophen 1,1-dioxide,289 and its 2-bromo289 and 2-methyl derivatives.290 All four possible dimers were obtained on irradiation of thio-chromone in aromatic solvents,291 and 1-thiauracil (345) is converted into... 

The pyrylium salts (76) are the six-membered oxygen heteroaromatic compounds. The 2- and 4-pyrones [(77) and (78) respectively] and the corresponding benzo analogues [coumarins (79) and chromones (80)] are represented by examples which further illustrate the usefulness of retrosynthetic analysis in the derivation of preparative methods. 

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. 

Chromone carbaldehyde 407 reacts with o-benzoquinodimethane 408 in a Diels-Alder reaction and concomitant deformylation to give a diastereomeric mixture of tetrahydrobenzo[ ]xanthones 409. Subsequent oxidation provides benzo[ ]xanthones 410 in good yields (Scheme 67) <2002T997>. 

Chromone-3-carbaldehydes undergo Diels-Alder reactions with ort o-benzoquinodimethane 819 and deformyla-tion to yield initially benzo[b]-1,6,6a, 12a-tetrahydroxanthones 820, which are easily transformed into their corresponding benzo[ ]xanthones upon treatment with I2-DMSO (Scheme 232) <2002T105>. 

The pyrilium cation 9.1, 2-pyrone 9.2, 4-pyrone 9.3, and their benzo-fused analogues the benzopyrilium cation 9.4, coumarin 9.5, chromone 9.6, are the parent structures of a series of six-membered ring heterocycles containing one oxygen atom. The impetus for research in this area comes from the enormous number of plant-derived natural products based on the benzopyrilium, coumarin, and chromone structures. 

An important difference between the monocyclic and benzo-fused series is that reactions with amines do not lead to the corresponding heterocycles in the benzo-fused series. For instance, aminolysis of chromone 9.29 affords phenol 9.30. Benzopyridone 9.32 is not produced. The facile tautomerisation between 9.25 and 9.26 would analogously give ketone 9.31 in this series. This high-energy intermediate is not aromatic, and the reaction stops at phenol 9.30. 

Benzo[fe]xanthene-6,l 1,12-triones are readily available through the photo-induced 1,4-acylation of naphthoquinone with 2-hydroxybenzaldehydes followed by oxidation <02H(57)1915>. Chromone-3-carboxaldehyde reacts with o-benzoquinodimethane in a DA reaction with concomitant deformylation to give a diastereoisomeric mixture of tetrahydrobenzo[fc]xanthones oxidation can be accomplished with DMSO/I2 <02T105>. 

Readily accessible 5-alkylidene-2,5-dihydropyrrol-2-ones 32 are transformed into functionalised pyran-4-ones on treatment with aq. HC1. The method is adaptable to the synthesis of dihydro- and tetrahydrochromones and benzo[/z]chromones <07T12975>. 

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