Benzyl alcohols, substituted

A crystalline derivative of benzyl alcohol cannot be obtained by using benzoyl chloride, because the benzyl benzoate, C HiCOOCHiCaHj, so obtained has m.p. 18°, and is thus usually liquid the present preparation illustrates therefore the use of a substituted benzoyl chloride (p-nitrobenzoyl chloride, m.p. 75°) in order to obtain a crystalline derivative of suitably high m.p. 

C) Carboxylic adds For aryl-substituted alcohols, such as benzyl alcohol, oxidation readily gives the corresponding add (c/. p. 336). 

Substitution Reactions on Side Chains. Because the benzyl carbon is the most reactive site on the propanoid side chain, many substitution reactions occur at this position. Typically, substitution reactions occur by attack of a nucleophilic reagent on a benzyl carbon present in the form of a carbonium ion or a methine group in a quinonemethide stmeture. In a reversal of the ether cleavage reactions described, benzyl alcohols and ethers may be transformed to alkyl or aryl ethers by acid-catalyzed etherifications or transetherifications with alcohol or phenol. The conversion of a benzyl alcohol or ether to a sulfonic acid group is among the most important side chain modification reactions because it is essential to the solubilization of lignin in the sulfite pulping process (17). 

Dimethoxybenzyl esters prepared from the acid chloride and the benzyl alcohol are readily cleaved oxidatively by DDQ (CH2CI2, H2O, rt, 18 h, 90-95% yield). A 4-methoxybenzyl ester was found not to be cleaved by DDQ. The authors have also explored the oxidative cleavage (ceric ammonium nitrate, CH3CN, H2O, 0°, 4 h, 65-97% yield) of a variety of 4-hydroxy- and 4-amino-substituted phenolic esters. ... 

C-Substitution Reactions of Silylated Allyl or Benzyl Alcohols... 

This is consistent with the observed products of oxidation, i.e. benzyl alcohol, benzaldehyde and benzoic acid and with the observed oxidation of cyclohexane. Radical-cations are, however, probably formed in oxidation of napthalene and anthracene. The increase of oxidation rate with acetonitrile concentration was intepreted in terms of a more reactive complex between Co(III) and CH3CN. The production of substituted benzophenones at high CH3CN concentration indicates the participation of a second route of oxidation. 

Loss of catalytic activity resulting from internal displacements is not usually a serious problem below temperatures of about 100 C. However, highly active R-groups, such as benzyl, methyl and allyl, undergo internal displacement more readily, particularly in the presence of strong nucleopfiles. For instance, the presence phenolates and thiolates may lead to the formation of benzyl alcohol, ethers, or sulphides from benzyl-substituted quaternary ammonium salts. 

Furfuryl alcohol in an acid medium gives rise to reactions of polycondensation reactions of successive electrophilic substitutions involving furan molecules. This reaction is identical to the reaction described for benzyl alcohol on p.256 and represents the same dangers. It is carried out under the same conditions, ie in a sulphuric medium. The electrophilic species that comes into play is very similar to the benzyl cation. 

Synthetic routes that access appropriately substituted thienobenzazepines are also quite important for medicinal chemistry stracture activity relationship studies, and many involve similar bond connectivity strategies. One notable example employs the use of conunercially available 4-methyl-3-nitrophenol (Scheme 6.3). Methylation of the phenol followed by bromination, hydrolysis, and oxidation of the benzylic alcohol afforded aldehyde 9 in quantitative yield. Treatment of this aldehyde with 5-lithio-2-methylthiophene provided, after dehydroxylation, nitro intermediate A in good overall yield. Reduction of the nitro functionality and treatment with phosgene presented the corresponding isocyanide which upon cychzation using aluminum trichloride in a Friedel-Crafts fashion afforded the... 

The low yields, which are observed among styrenyl adducts, reflect a combination of the poor reactivity of the styrene at the low temperature of the reaction. For example, the combination of t-butyl Grignard with the 2,4-bis-OBoc-benzyl alcohol 15 affords the corresponding benzopyran 50 in only 50% yield even when carried out in the presence of 5-10 equivalents of the styrene (method H, Fig. 4.27).27 Yields for substituted benzopyran styrene adducts are still lower (method G, Fig. 4.27). For example, addition of methyl lithium to 2,4-bis-OBoc-benzylaldehyde 5 followed by the addition of the dienophile and magnesium bromide affords benzopyran 51 in a paltry 27% yield. Method F is entirely ineffective in these cases, because the methyl Grignard reagent competes with the enol ether and with styrene 1,4-addition of methyl supercedes cycloaddition. 

The use of the phenyl phosphate group as both a solid support attachment site and a crucial binding element represents what has been referred to as a pharmacophore-linking strategy [26]. We explored a variety of phenyl phosphate tether functionalities to provide resins varying in substitution pattern and in chemical flexibility (Scheme 1 and Table 4) [22]. All phenyl phosphate resins were synthesized in batch quantities of 20 g or more. Resin synthesis began with the addition of either /mnethoxy-benzyl alcohol or benzyl alcohol to commercially available bis(diisopro-pylamino)chlorophosphine, followed by addition of the diversity phenol [(Ri)-OFl, DIAT (diisopropylamino tetrazole)]. Displacement of the... 

Table 5 Reaction of an ori/zo-substituted aryl iodide with benzyl alcohol in the presence of K2C03, Pd(OAc)2 and norbomene.1...

General procedure for the reaction of an o-substituted aryl iodide in the presence of benzyl alcohol. Synthesis of biphenyl derivatives. 

In a related study involving structurally similar chiral methylzinc anisyl fencholates, both chiral amplification and depletion were observed in the catalytic alkylations of benzaldehyde.209 Thus, methylzinc anisyl fencholates, bearing sterically small substituents in the ortho-position of the anisyl group, crystallized preferentially as homochiral dimers, as shown for the methyl-substituted anisyl group in Scheme 91. Because of the greater stability of the homochiral dimers, scalemic mixtures of both enantiomers of the ligand showed a chiral depletion of the benzyl alcohol. 

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