Carbonyl group aromatic substitution

Several reports of the synthesis and chemistry of benzimidazoles have been published. The most common methods involved the condensation of 1,2-phenylenediamine with a carbonyl group. 2-Substituted benzimidazoles were prepared from 1,2-phenylenediamine and esters under microwave conditions <06SC2597>. A highly selective synthesis of 2-aryl-l-arylmethyl-l/7-1,3-benzimidazoles from the reaction of 1,2-phenylenediamines and aromatic aldehydes in the presence of silica sulfuric acid in ethanol or water has been reported <06TL2557>. Microwave-assisted one-step high-throughput synthesis of benzimidazoles from phenylenediamine and carboxylic acids in the presence of triphenyl phosphite has been disclosed <06TL2883>. A... 

The carbonyl group (aromatic aldehydes, ketones, adds, and esters) is deactivating and -directing. There are distinct limitations on the types of substitutions that are satisfactory with carbonyl-substituted aromatics. In general, only those electrophiles in the first group in Scheme 9.1 react readily. 

Hammen equation A correlation between the structure and reactivity in the side chain derivatives of aromatic compounds. Its derivation follows from many comparisons between rate constants for various reactions and the equilibrium constants for other reactions, or other functions of molecules which can be measured (e g. the i.r. carbonyl group stretching frequency). For example the dissociation constants of a series of para substituted (O2N —, MeO —, Cl —, etc.) benzoic acids correlate with the rate constant k for the alkaline hydrolysis of para substituted benzyl chlorides. If log Kq is plotted against log k, the data fall on a straight line. Similar results are obtained for meta substituted derivatives but not for orthosubstituted derivatives. 

Because the carbon atom attached to the ring is positively polarized a carbonyl group behaves m much the same way as a trifluoromethyl group and destabilizes all the cyclo hexadienyl cation intermediates m electrophilic aromatic substitution reactions Attack at any nng position m benzaldehyde is slower than attack m benzene The intermediates for ortho and para substitution are particularly unstable because each has a resonance structure m which there is a positive charge on the carbon that bears the electron withdrawing substituent The intermediate for meta substitution avoids this unfavorable juxtaposition of positive charges is not as unstable and gives rise to most of the product... 

Polyfluoroalkyl- andperfluoroalkyl-substituted CO and CN multiple bonds as dipolarophiles. Dmzo alkanes are well known to react with carbonyl compounds, usually under very mild conditions, to give oxiranes and ketones The reaction has been interpreted as a nucleophilic attack of the diazo alkane on the carbonyl group to yield diazonium betaines or 1,2,3 oxadiazol 2 ines as reaction intermediates, which generally are too unstable to be isolated Aromatic diazo compounds react readily with partially fluorinated and perfluorinated ketones to give l,3,4-oxadiazol-3-ines m high yield At 25 °C and above, the aryloxa-diazolines lose nitrogen to give epoxides [111]... 

As the preceding examples indicate, the yields of these SOCI2 and PBr3 reactions are generally high, and other functional groups such as ethers, carbonyls, and aromatic tings don t usually interfere. We ll look at the mechanisms of these substitution reactions in the next chapter. 

The way in which various substituents affect the polarization of a carbonyl group is similar to the way they affect the reactivity of an aromatic ring toward electrophilic substitution (Section 16.5). A chlorine substituent, for example, inductively withdraws electrons from an acyl group in the same way that it withdraws elections from and thus deactivates an aromatic ring. Similarly, amino, methoxvl, and methylthio substituents donate electrons to acyl groups by resonance in the same way that they donate electrons to and thus activate aromatic rings. 

In simple aromatic amides, fragmentation occurs on both sides of the carbonyl group. If a hydrogen is available in iV-substituted aromatic amides, it tends to migrate and form an aromatic amine... 

The nucleophilic aromatic substitution reaction for the synthesis of poly(arylene ether ketone)s is similar to that of polysulfone, involving aromatic dihalides and aromatic diphenolates. Since carbonyl is a weaker electron-withdrawing group titan sulfonyl, in most cases, difluorides need to be used to afford high-molecular-weight polymers. Typically potassium carbonate is used as a base to avoid the... 

Since aromatic substitutions, aliphatic substitutions, additions and conjugate additions to carbonyl compounds, cycloadditions, and ring expansion reactions catalyzed by Fe salts have recently been summarized [17], this section will focus on reactions in which iron salts produce a critical activation on unsaturated functional groups provided by the Lewis-acid character of these salts. 

It has also been known for many years that sulfonyl groups, like carbonyl groups, promote the addition of nucleophilic reagents to carbon- carbon double bonds . The meta-directing properties of the S02Me group in electrophilic aromatic substitution were discovered in the mid-1920s . ... 

H-bonding occurs intramolecularly between ortho-substituted donors and acceptors like in o-nitrophenol. In terms of H-bonding between aromatic ortho substituents, the octanol-water system seems to be sensihve to a very restricted class. The only clear-cut cases result from a carbonyl group directly attached to the ring acting... 

Nucleophilic substitution reactions, to which the aromatic rings are activated by the presence of the carbonyl groups, are commonly used in the elaboration of the anthraquinone nucleus, particularly for the introduction of hydroxy and amino groups. Commonly these substitution reactions are catalysed by either boric acid or by transition metal ions. As an example, amino and hydroxy groups may be introduced into the anthraquinone system by nucleophilic displacement of sulfonic acid groups. Another example of an industrially useful nucleophilic substitution is the reaction of l-amino-4-bromoanthraquinone-2-sulfonic acid (bromamine acid) (76) with aromatic amines, as shown in Scheme 4.5, to give a series of useful water-soluble blue dyes. The displacement of bromine in these reactions is catalysed markedly by the presence of copper(n) ions. 

A diverse group of organic reactions catalyzed by montmorillonite has been described and some reviews on this subject have been published.19 Examples of those transformations include addition reactions, such as Michael addition of thiols to y./bunsatu rated carbonyl compounds 20 electrophilic aromatic substitutions,19c nucleophilic substitution of alcohols,21 acetal synthesis196 22 and deprotection,23 cyclizations,19b c isomerizations, and rearrangements.196 24... 

Note that in this case, the three carbonyl ligands are staggered relative to the carbon atoms in the benzene ring (as indicated by the dotted vertical lines). Similar compounds have also been prepared containing Mo and W. Methyl-substituted benzenes such as mesitylene (1,3,5-trimethylbenzene), hexamethylbenzene, and other aromatic molecules have been used to prepare complexes with several metals in the zero oxidation state. For example, Mo(CO)6 will react with 1,3,5-C6H3(C]T3)3, 1,3,5-trimethylbenzene, which replaces three carbonyl groups. 

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