Heterocycles coumarins

Many fluorophores of practical interest are heterocyclic coumarins, rhodamines, pyronines, fluoresceins, oxazines, etc. A few examples will now be presented. 

Synthetic studies on heterocycles (coumarins, benzoxazoles, various alkaloids) 06YZ543. 

There is also a great, number of oxygen-containing heterocyclic compounds that fluoresce. Coumarins and flavonoids are the two largest classes of oxygen heterocycles. Coumarins fluoresce more intensely under basic conditions where flavones fluoresce weakly. In 30% sulfuric acid solution, flavones fluoresce intensely and coumarins do not. 

Many chemical compounds have been described in the Hterature as fluorescent, and since the 1950s intensive research has yielded many fluorescent compounds that provide a suitable whitening effect however, only a small number of these compounds have found practical uses. Collectively these materials are aromatic or heterocycHc compounds many of them contain condensed ring systems. An important feature of these compounds is the presence of an unintermpted chain of conjugated double bonds, the number of which is dependent on substituents as well as the planarity of the fluorescent part of the molecule. Almost all of these compounds ate derivatives of stilbene [588-59-0] or 4,4 -diaminostilbene biphenyl 5-membeted heterocycles such as triazoles, oxazoles, imidazoles, etc or 6-membeted heterocycles, eg, coumarins, naphthaUmide, t-triazine, etc. 

These observations indicated that an intermolecular double condensation to give a bis N-(methylene-4-oxocoumarinyl)-l,4 aromatic diamine had occurred. Data from the elemental analysis indicated that the calculated and observed values were within the acceptable limits ( 0.4%) and in conformity with the assigned structure. In the addition of molar equivalents of 1,4-aromatic binucleophilic compounds to compound 72 we did not observe any heterocyclic compounds resulting from the further intermolecular nucleophilic attack on the single condensation product. Since the condensation of 3-(dimethylaminomethylene)-chromane-2,4-dione with aromatic binucleophilic compounds is the only route to the new coumarinic compounds, this represents a useful synthetic method. 

Studies of fluorescence properties of the dye pair (i.e., boron difluoride complexes dye 9a-d and the nonsubstituted one lOa-d) in the BSA/SDS mixture revealed that coumarins 9b and 10c showed two excitation and emission bands, while other heterocycles showed single bands in the corresponding spectra. For all studied compounds, excitation and emission maxima occurred in the range 405-603 nm and 467-680 nm, respectively. 

Brufola G, Fringuelli F, Piermatti O, Pizzo F (1996) Simple and efficient one-pot preparation of 3-substituted coumarins in water. Heterocycles 43 1257-1266... 

Coumarins and related ring systems may be converted into benzo-fused tricyclic heterocycles by the simple transformations shown in Equations (113)—(116) <2003JHC249>. 

Reviews of saturated oxygen heterocycles <00JCS(P1)1291>, routes to 2,2-dimethyl-2H-[l]benzopyrans <00H(53)1193> and pyranonaphthoquinone antibiotics <00T1937>, HIV-1 active Calophyllum coumarins <00H(53)453> and of the application of (3-halovinylaldehydes in heterocyclic synthesis <00H(53)941> have appeared. 

The intramolecular version of this reaction provides a general method for the preparation of biologically active heterocycles such as coumarins, quinolinones, and thiocoumarins (yield, 50-91%) (Equation (48) and Table 2).47,47b The reaction tolerates various functional groups such as Br, GHO, etc. 

Because of its importance, the application of planar chromatography for the analysis of various secondary metabolites in plants such as heterocyclic oxygen compounds (coumarins, flavonoids, anthocyanins, etc.) has been reviewed many times [143,144],... 

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. 

Chromones differ marginally in their chemistry from coumarins (ben-zopyran-2-ones) because the carbonyl group is now conjugated with the oxygen atom via the double bond of the heterocycle (see Box 5.2). This conjugation does not involve the benzene ring. 

Coumarin. The coumarin moiety is found in a number of important drugs. This is a bicyclic heterocycle containing two six-membered rings and two oxygens, one endo-cyclic, one exocyclic. Since the coumarin contains an intramolecular lactone ester, it undergoes hydrolysis to yield a carboxylic acid and a phenol. 

The analogous palladium catalyzed reaction of internal acetylenes, 2-iodophenol and carbon monoxide leads to the selective formation of coumarins. The heterocyclic analogues of o-iodophenol are also effective. The o-iodopyridone shown in 4.16. for example gave rise to the formation of azacoumarin in 70% yield.18 In these processes the insertion of the acetylene derivative occurs in advance of the insertion of CO. Interestingly, the change of the acetylene to an alkene reverses the insertion order and leads to flavone formation.19... 

In some instances, especially with the oxygen and sulfur heterocycles, the overall reaction leading to a substituted product does not involve an SEAr mechanism but proceeds by an addition followed by elimination sequence, as outlined for the bromination of coumarin in equation (4). The choice of experimental conditions can affect the outcome of the reaction, as illustrated in the formation of (114) and (115) in Section 3.2.1.4.7. 

In complex heterocyclic compounds, the terms coumarano, couma-rono, coumarino are therefore rejected, although they allow a shortening of the occasionally somewhat cumbersome and forbidding Chemical Abstracts nomenclature thus, coumestrol (4) will not be called the dihydroxy derivative of coumarono[3,2-c]coumarin,7 but 3,9-dihydroxy-6 -benzofuro[3,2-c][ l]benzopyran-6-one. 

In the second group the starting molecule belongs to another class of oxygenated heterocycle, such as a coumarin, flavone, chroman, a,fi-unsaturated y-lactone, or S-sultone. 

Two failures of the Perkin reaction should be reported 5-nitro-coumarin gives a 3,4-dibromide, but alkaline treatment does not lead to 5-nitrocoumarilic acid,812 further, 2//-naphtho[l, 2-6]pyran-2-one (366) is brominated not on the heterocycle, but in position 6.813... 

The available evidence suggests that the heterocyclic ring in compounds (19), (28) and (206) is not markedly aromatic. Much of the chemistry of coumarins can be rationalized in terms of a benzo-fused enol lactone structure. 

As with pyran-2-one, the NMR spectra of coumarins indicate some degree of charge delocalization. However, the aromaticity of the heterocyclic ring is only marginal. 

The synthesis of chromenes from other six-membered oxygen heterocycles has much to offer because of the accessibility of the precursors. Thus much of the earlier work on chromenes was based especially on their synthesis from coumarins or chromanols. 

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