Hydrogen atoms, activated, substitution

A white solid, m.p. 178 C. Primarily of interest as a brominaling agent which will replace activated hydrogen atoms in benzylic or allylic positions, and also those on a carbon atom a to a carbonyl group. Activating influences can produce nuclear substitution in a benzene ring and certain heterocyclic compounds also used in the oxidation of secondary alcohols to ketones. 

In order to allow any multiple chlorination of the biphenyl skeleton, the user may define an atom list (eonsisting of hydrogen and chlorine atoms) and substitute all H-atoms by this list. One may click on the drop-down selection box behind the element icons, select the options Generics. .set the user-defined atom to A1 and quit by the OK button. As a result this atom selection is active for the subsequent drawing steps. After this atom list is drawn ten times as the ten substituents, its composition has to be defined by clicking the A, icon on the left-hand side of the structure editor and by selecting H and Cl in the periodic table (Figure 5-16). 

A radically different course is followed when the reaction of 2-alkyl-substituted thiazoles is periormed in methanol or acetonitrile (335), 2 1 adducts containing seven-membered azepine rings (91) are being formed in which two of the original activated hydrogen atoms have altered positions (Scheme 55). A similar azepine adduct (92) was obtained by... 

With active methylene compounds, the carbanion substitutes for the hydroxyl group of aHyl alcohol (17,20). Reaction of aHyl alcohol with acetylacetone at 85°C for 3 h yields 70% monoaHyl compound and 26% diaHyl compound. Malonic acid ester in which the hydrogen atom of its active methylene is substituted by A/-acetyl, undergoes the same substitution reaction with aHyl alcohol and subsequendy yields a-amino acid by decarboxylation (21). 

The effect substitution on the phenolic ring has on activity has been the subject of several studies (11—13). Hindering the phenolic hydroxyl group with at least one bulky alkyl group ia the ortho position appears necessary for high antioxidant activity. Neatly all commercial antioxidants are hindered ia this manner. Steric hindrance decreases the ability of a phenoxyl radical to abstract a hydrogen atom from the substrate and thus produces an alkyl radical (14) capable of initiating oxidation (eq. 18). 

Although some authors propose that an enolizable /3-dicarbonyl system is essential for inflammatory activity, two analogues in which this hydrogen atom at carbon 4 has been substituted, suxibuzone (717) and pipebuzone (718), are used as antiinflammatory agents, and the latter also possesses antipyretic and analgesic properties. However, these compounds are probably not active per se and their activity is due to metabolism to phenylbutazone. 

When a hydrogen atom is peri to an azine-nitrogen, there is no steric inhibition of resonance activation as there is in 1-nitronaph-thalene (4-methoxy-dechlorination of its 4-chloro derivative seems to be thereby decelerated only 2-fold in rate). Steric hindrance of nucleophihc substitution by the co-planar peri hydrogen is sometimes... 

The presence of active oxygen will activate a hydrogen atom in a position. This can give rise to dangerous substitution reactions because of their exo-thermicity and above all the instability of the products obtained. The danger is even higher if the carbon chain is broken. 

Complex 4a (see Fig. 1) differs from these catalytically active complexes only in the substitution of the complexed olefin molecules and hydrogen atom by a 7r-allyl group. The ligands in these square-planar molecules can adopt two different arrangements around the central nickel atom The olefin can either be trans (31a) or cis (31b) to the phosphine molecule. Because precedent exists for both these arrangements [e.g., 12 (84) and 30 (82)]. it is difficult to decide which of the two structures (31a or 31b) represents the catalytically active species. It is of course possible that the differences observed in the catalytic properties of systems having different ligands L and Y (Section IV) is due (at least in part) to differences in the population of 31a and 31b. 

A very impressive example of the synthetic utility of this chemistry is the one-pot enantioselective double G-H activation reaction of 86 to generate chiral spiran 87 (Equation (73)).172 In this case, the phthalimide catalyst Rh2(enantiotopically selective aromatic C-H insertions of diazo ketoesters (Equation (74)).216 Moreover, dirhodium(n) tetrakisIA-tetrafluorophthaloyl- )-/ /-leucinate], Rh2(hydrogen atoms of the parent dirhodium(n) complex are substituted by fluorine atoms, dramatically enhances the reactivity and enantioselectivity (up to 97% ee). Catalysis... 

Enantioselective synthesis of /1-amino acids is important as they are present in various natural products and in many biologically active compounds [26,27]. Several methods exist for the enantioselective synthesis of -substituted /1-amino acids (/l3-amino acids) however, synthesis of a-substituted /1-amino acids (/l2-amino acids) is very limited [28,29]. A report on highly enantioselective hydrogen atom transfer reactions to synthesize /l2-amino acids (Scheme 9) has recently been described [30]. 

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