Benzylic hydrogen replacement

Lead tetrafluoride, generated in situ from lead dioxide and hydrogen fluonde, can replace benzylic hydrogen by fluonne [3] Under sirmlar conditions phenol is simultaneously oxidized to 4,4-difluoro-2,5-cyclohexadienone [4 (equations 3 and 4)... 

Vanadium pentafluoride replaces benzylic hydrogen by fluonne but also adds fluonne to the aromatic system, giving fluonnated cyclohexadienes and cyclohexenes [5] (equation 5)... 

This conversion has been used as a key step in the preparation of optically active aziridines from optically active 1,2-diols (prepared by 15-46). ° Even hydrogen can be the leaving group. Benzylic hydrogens have been replaced by N3 by treatment with HN3 in CHCI3 in the presence of DDQ (p. 1511). °°... 

In an extension to the xanthenyl theme, the benzyl hydrogen was replaced with a substituted / -methoxyphenyl ring to give linker 35 (Scheme 10) [41]. Peptide amides were cleaved rapidly and in high purity with TFA-DCM (1 9) for 15 min or as a protected fragment with TFA-DCM (1 99) for 3-10 min. 

The benzylic hydrogen atom of alkylarenes is replaced by the azido group on treatment with trimethylsilyl azide in the presence of 2,3-dichloro-5,6-dicyano-l,4-benzoquinone subsequent hydrogenation yields amines (e.g. equation 5)31. 

Catalysts and reaction conditions used are generally similar to those used for olefin isomerization. Catalysts reported are sodium-organosodium catalysts prepared in situ by reaction of a promoter such as o-chloro-toluene or anthracene with sodium 19-24), alkali metal hydrides 20,21), alkali metals 22), benzylsodium 26), and potassium-graphite 26). These catalysts are strong bases that can react with alkylaromatics to replace a benzylic hydrogen [Reaction (2)]. 

Of the olefins, ethylene has been most extensively studied (19, 21, 23-26, 36) it reacts most readily in base-catalyzed alkylations. In general temperatures of 150-200 are used with relatively low ethylene pressures (0-70 atm.). Benzylic hydrogens are replaced by ethyl groups i.e., toluene yields n-propylbenzene. Additional substitution on the a-carbon may yield 3-phenylpentane and 3-ethyl-3-phenylpentane [Reaction (3)]. 

Thus ethyl groups may be added to a-carbons as long as benzylic hydrogens are available for replacement. The mechanism which has been proposed by Pines et al. 19) for the reaction consists of the addition of the benzylic carbanion formed by reaction of the aromatic and the catalyst with the olefin followed by a transmetalation reaction with more of the aromatic [Reaction (4)]. 

The reaction of alkylbenzenes with ethylene in the presence of sodium occurs with successive replacement of one or two benzylic hydrogens to produce mono-and diethylated compounds.235 Propylene reacts to form isomeric products with the preponderance of the branched isomer236 [Eq. (5.61)]. When potassium is used as catalyst, indan derivatives can also be formed237 [Eq. (5.62)] ... 

Substrates that carry a replaceable benzylic hydrogen atom, or a similar hydrogen that gives rise to a stabilized radical, can be selectively chlorinated or brominated. Ethylbenzene leads to only... 

Chlorination.1 C120 is particularly useful for side-chain chlorination of deactivated aromatic substrates by a free-radical process involving CIO . Although it cun be used to convert methylarenes to mono- and dichloromethyl derivatives, it is particularly useful for conversion to trichloromethylarenes. Thus it converts p-nitrotoluene into p-nitrobenzotrichloride in 99.8% yield. It is also useful for selective replacement of benzylic hydrogens. 

Alkylaryl azides.3 Reaction of an alkylarene with DDQ and N3Si(CH3)3 in CHC13 at 25° results in replacement of a benzylic hydrogen by an azide group to give an alkylaryl azide in 50-95% yield. Hydrazoic acid can be used in place of azidotrimethylsilane, but this reaction is generally slower. 

As described in the previous section, substitution at the benzylic position always takes place together with nuclear substitution if the aromatic substrates possess replaceable benzylic hydrogens (equation 39). Benzylic alcohols, esters and ethers can all be oxidized at the benzylic position to yield the corresponding carbonyl compounds. ... 

Ethylation of alkylbenzene proceeds at 150° to 200° with ethylene pressure ranging from 1 to 70 atm. The reaction involves the replacement of benzylic hydrogens by ethyl groups,... 

Benzyl Hydroxyl Amine.—One of the hydroxyl amines of the benzene homologues is of importance in illustrating a case of isomerism. The compound is the hydroxyl amine derivative of toluene with the hydroxyl amine group substituted in the side chain, i.e., it is benzyl hydroxyl amine. The isomerism is due to the different hydrogen atoms of the hydroxyl amine which the benzyl group replaces. The two compounds are ... 

In the alpha compound the benzyl group replaces the hydroxyl hydrogen of hydroxyl amine while in the beta compound it replaces one of the amino hydrogens. There are also known two isomeric di-benzyl hydroxyl amines and one tri-benzyl hydroxyl amine. 

More frequently, the benzylic hydrogen is replaced by an acyloxy group on refluxing with ceric ammonium nitrate in 100% acetic acid [415], with lead tetraacetate [434, 437], or with lead tetrakis(trifluoroacetate) [435]. 

The substitution pattern for the benzylic carbon is quite simple. Replacing the benzylic hydrogens decreases activity. Polar groups eliminate activity. This can be seen in Table III. 

Structure-Activity Relationships. Effects caused by initial structural modifications in the lead compound are shown in Table I. Replacement of the oxygen in 1 with sulfur caused complete loss of activity. Replacement of the phenyl moiety at the 2-position with benzyl, hydrogen, or alkyl gave inactive analogs ( -9 Similary, replacement of N-phenyl with hydrogen, alkyl,... 

C=N, The benzyl group is a toluene molecule with a hydrogen replaced, as depicted below. 

Trimethylsilyl azidel2,3-dichloro-5,6-dicyanoquinone Replacement of benzylic hydrogen by prim, amino via azido groups... 

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