Substituent effects hydroxy groups

The effect of substituents on the reactivity of heterocyclic nuclei is broadly similar to that on benzene. Thus mem-directing groups such as methoxycarbonyl and nitro are deactivating. The effects of strongly activating groups such as amino and hydroxy are difficult to assess since simple amino compounds are unstable and hydroxy compounds exist in an alternative tautomeric form. Comparison of the rates of formylation and trifiuoroacetylation of the parent heterocycle and its 2-methyl derivative indicate the following order of sensitivity to substituent effects furan > tellurophene > selenophene = thiophene... 

The acetoxy dienone (218) gives phenol (220). Here, an alternative primary photoreaction competes effectively with the dienone 1,5-bonding expulsion of the lOjS-acetoxy substituent and hydrogen uptake from the solvent (dioxane). In the case of the hydroxy analog (219) the two paths are balanced and products from both processes, phenol (220) and diketone (222), are isolated. In the formation of the spiro compound (222) rupture of the 1,10-bond in the dipolar intermediate (221) predominates over the normal electron transmission in aprotic solvents from the enolate moiety via the three-membered ring to the electron-deficient carbon. While in protic solvents and in 10-methyl compounds this process is inhibited by the protonation of the enolate system in the dipolar intermediate [cf. (202), (203)], proton elimination from the tertiary hydroxy group in (221) could reverse the efficiencies of the two oxygens as electron sources. 

Anthocyanins and anthocyanidins, compounds present with high structural diversity in fruits and wines, showed a pattern as antioxidants different from that of the tea catechins with respect to the effect of substituents. In a liposomal model system induced peroxidation was inhibited increasingly by anthocyanins/ anthocyanidins with an increasing number of hydroxyl groups in the B-ring (Fig. 16.6), while the opposite was seen for the catechins (Seeram and Nair, 2002). For anthocyanidins, the presence of a 3-hydroxy group is important... 

Methylation of N,N-dimethyltryptamines at either the 1-, 2-, or 6-position decreases potency, while methylation at the 5- or 7-position seems to have relatively little effect on activity. The 4-hydroxy derivatives of DMT appear to be the only hydroxy compound to show appreciable activity. The 5-, 6-, and 7-hydroxy isomers are either less active or inactive. Methylation of these hydroxy groups to yield the corresponding methoxy derivatives has different effects, depending on the position of the substituent. Methylation of the 4-hydroxy group decreases potency, while methylation of the 5-hydroxy group increases activity dramatically. The 6- and 7-methoxy derivatives are less active than either the 4- or 5-methoxy isomers. 

Stereoselective cyclization controlled by a substituent remote from the reaction center is often difficult to achieve. However, 1-mediated cyclization of the substrates illustrated in Eq. 9.54 proceeds in a highly stereoselective manner when the hydroxy group is converted to a magnesium alkoxide prior to cyclization [99,100]. The effect of the alkoxide group is much more favorable than that of the corresponding TBS ether. 

Of the various anthracenedione isomers, only the 9,10-compound is used for the synthesis of dyes it is usually referred to simply as anthraquinone (6.1). The parent compound is pale yellow in colour, having a weak absorption band in the visible region (n—>tt transition). The presence of one or more electron-donating substituents leads to significant bathochromic effects so that relatively simple derivatives are of commercial importance as dyes. The colour of such compounds, which usually contain amino or hydroxy groups, can be attributed to the existence of a charge-transfer absorption band [1]. 

Bis [(trifluoromethyl)thio] acetaldehyde (83a) has been prepared from an enam-ine precursor (84), although refluxing in aqueous ethanolic HCl is required to effect this reaction.The aldehyde is less stable than its enol tautomer (83b), and many reactions typical of aldehydes fail. For example, addition of aqueous silver nitrate immediately yields the silver salt of (83b), rather than giving precipitation of (elemental) silver. The (trifluoromethyl)thio substituent has pseudohalogenic character and, together with the hydroxy group, stabilizes the alkene tautomer in the manner of a push-pull alkene. The enol-aldehyde equilibrium mixture in acetonitrile shows an apparent of 2.6 when titrated with aqueous hydroxide. 

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