Dihydrocoumarin, from coumarin

Dihydrocoumarins are available from coumarins bearing an electron-withdrawing group at the 3-position by the selective reduction of the 3,4-double bond by 1,4-dihydropyridines (Scheme 32) <06S771>. 

Asymmetric syntheses of warfarin <96TL8321> and the axially chiral bicoumarin, isokotanin A <96TL3015> have been reported. The former is based on a Rh-catalysed asymmetric hydrogenation of a 3-(a,P-unsaturated ketone) substituted coumarin, whilst the key steps of the latter are an asymmetric Ullmann coupling and a selective demethylation. The stereochemistry of the fused dihydrocoumarin resulting from Li/NHs reduction of... 

Apart from glucuronic acid and sulfate conjugation of hydroxycoumarins, other phase II pathways of coumarin metabolism have been identified. For example, ortho-coumaric acid may be conjugated with glycine (Lake, 1999), and a coumarin mercapturic acid conjugate has also been reported (Huwer et al., 1991). Coumarin may also be metabolized by the gastrointestinal microflora to 3,4-dihydrocoumarin and ort/io-hydroxyphenylpropionic acid under anaerobic conditions (Scheline, 1968). 

There is a similarity in mass spectral behaviour between dihydrocoumarin (23) and coumarin itself, since both decompose by two successive losses of carbon monoxide from the molecular ion. However, unlike coumarin, the formation of an [RDA]t ion at m/e 106 by elimination of ethylene also occurs (64AJC975). 

Benzocoumarins (405) result from the dehydrogenation of the corresponding dihydrocoumarins by palladium-charcoal at 300 °C in the absence of solvent (73CB62), whilst 4-aryl-3,4-dihydrocoumarins are converted to the coumarins in diphenyl ether (72IJC32). This latter conversion also occurs under milder conditions using iodine and potassium acetate in acetic acid (73AJC899). 

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. 

DBU-CCI4 and DBU-CBrClj proved to be mild oxidation reagents for compounds containing active hydrogens (85MI7). Thus, a-diketones, disulfides and coumarin were obtained in high yields from a-ketols, thiols, and 3,4-dihydrocoumarin, respectively, under mild conditions. 

Electrochemical reduction of coumarin [187] affords the meso and ( ) forms of a product hydrodimerized (at C-4) like many other a,)6-unsaturated acid derivatives. In the presence of tertiary amines, which are not destroyed during the process but catalyze the evolution of hydrogen, a transfer of hydrogen takes place from the amine radical to the coumarin radical with formation of 3,4-dihydrocoumarin. Asymmetric amines cause asymmetric induction during the reduction of 4-methylcoumarin, as in Chapter 26 [188]. 

Reduction of coumarins to the dihydro-derivatives has frequently been achieved, but a more efficient procedure has emerged from a new study of this conversion. The most effective method was catalytic reduction in ethanol at 150 °C and under a high pressure (1500 psi) of hydrogen of give mostly the 2-hydroxy-3-phenylbutanoate, which was readily cyclized with PPA to the dihydrocoumarin. Hydroboration of 3-arylcoumarins, followed by oxidation, gave isoflavanones the latter have been dehydrogenated (with DDQ) to isoflavones. A reaction of wide potential value is the selective hydrolysis by zinc and methanol of phenolic acetates in the presence of aUphatic acetate groups. 

In the synthesis of coumarins by the von Pechmann reaction, a spiro-compound (251) was simultaneously formed from 4-chloro-2-methylphenol (and from 2,3,5-trimethylphenol). A possible mechanism for this reaction involves the formation of the lactone (252), which reacts with another molecule of the phenol. The condensation of the dicyano-ester (253) [obtained from malononitrile and ethyl cyanoacetate] with substituted o-hydroxybenzaldehydes yields substituted coumarinimines, e.g. (254).A series of 4,6,7-substituted coumarins have been prepared and assessed for their suitability in fluorescence labelling of polymers. Esters of the type PhCH CRCOaAr react with AICI3 to give coumarins, which are probably formed via dihydrocoumarins (255) by dearylation. ... 

KIO is also effective in the synthesis of coumarins from phloroglucinol and 3-arylpropynoyl chlorides and of 3,4-dihydrocoumarins using cinnamoyl chlorides. At high... 

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