Alcohols, Phenols, and Carboxylic Acids

Me3SiCH2CH=CH2i TsOH, CH3CN, 70-80°, 1-2 h, 90-95% yield. This silylating reagent is stable to moisture. Allylsilanes can be used to protect alcohols, phenols, and carboxylic acids there is no reaction with thiophenol except when CF3S03H is used as a catalyst. The method is also applicable to the formation of r-butyldimethylsilyl derivatives the silyl ether of cyclohexanol was prepared in 95% yield from allyl-/-butyldi-methylsilane. Iodine, bromine, trimethylsilyl bromide, and trimethylsilyl iodide have also been used as catalysts. Nafion-H has been shown to be an effective catalyst. 

Trimethylsilyl cyanide. This reagent readily silylates alcohols, phenols, and carboxylic acids, and more slowly, thiols and amines. Amides and related compounds do not react with this reagent. The reagent has the advantage that a volatile gas (HCN is highly toxic) is the only byproduct. 

Me3Si0C(0)NMe2. This reagent produces volatile byproducts and autocatalytically silylates alcohols, phenols, and carboxylic acids. 

Hydrogens on carbon next to a carbonyl group are acidic. In general, a /3-dicarbonyl compound is most acidic, a ketone or aldehyde is next most acidic, and a carboxylic acid derivative is least acidic. Remember that alcohols, phenols, and carboxylic acids are also acidic because of their -OH hydrogens. 

Kulikov, A. Arumugam, S. Popik, V. V. Photolabile protection of alcohols, phenols, and carboxylic acids with 3-hydroxy-2-naphthalenemethanol. J. Org. Chem. 2008. 73, 7611-7615. 

Nafion-H has been shown to be effective in a variety of protection-deprotection reactions including (9-trialkylsilylation of alcohols, phenols, and carboxylic acids, as well as the preparation and methanolysis of tetrahydropyranyl (THP) ethers.672 However, when compared, for example, with HBF4-silica or Nafion nanocomposites,... 

A simple process for the trimethylsilylation of alcohols, phenols, and carboxylic acids in refluxing CH2C12 over Nafion-H has been reported by Olah et al.672 [Eq. (5.240)]. The transformation of phenols and carboxylic acids requires higher temperature (CCI4 reflux). 

The strong catalytic effect of amines in silylation with silyl hydrides of some protic substrates, like alcohols, phenols, and carboxylic acids, is well known (for review, see Ref. 316). In this case, the amine is not likely to ionize the silicon-leaving group bond. General base catalysis has been... 

The commonest compounds containing O—H bonds are water, alcohols, phenols and carboxylic acids (if inorganic acids and bases are neglected). Hydrogen atom transfer from water to a radical seems to be unknown (Kondratiev, 1970 Bennett et al., 1970 for deuterium atom transfer from D20 to N see Felder et al., 1970). 

The Si, Ge, Sn containing N4-chelates (6J)-(66) react with monovalent alcohols, phenols and carboxylic acids to the corresponding alkoxides, aroxides and carbox-ides Polymers were prepared with analc ous bivalent comonomers. 

The reaction of oxygen-containing nucleophiles including alcohols, phenols, and carboxylic acids allows the generation of a 1,2-diol equivalent in which the oxygen atoms are differentially protected. Given the synthetic utility of 1,2-diols... 

Another facile silylating reagent for hydroxyl groups of alcohols, phenols and carboxylic acids is N,0-bis(TMS)-carbamate (716) which gives yields between 85-95%, and only ammonia and carbon dioxide are the by-products (equation 364)399. 

Silylation. This is an efficient silyl donor in fact, it is superior to N,0-bis(trimethylsilyl)acetamide (1, 61 2, 30 3, 23-24) or to N,0-bis(trimethylsilyl) carbamate, (CH3)3SiNHC02Si(CH3)a. Yields of silylated alcohols, phenols, and carboxylic acids are 92-987o- The by-product, sulfamic acid, is insoluble in the medium and removable by filtration. 

So now we can expand our chart of acid and base strengths to include the important classes of alcohols, phenols, and carboxylic acids. They conveniently, and memorably, have piCa values of about 0 for the protonation of alcohols, about 5 for the deprotonation of carboxylic acids, about 10 for the deprotonation of phenols, and about 15 for the deprotonation of alcohols. The equilibria above each piCa shows that at approximately that pH, the two species each form 50% of the mixture. You can see that carboxylic acids are weak acids, alkoxide ions (RO ) are strong bases, and that it will need a strong acid to protonate an alcohol. 

Although alcohols, phenols, and carboxylic acids each have special aracteristics, we shall consider these compounds together in this section because many published studies have examined these compounds as a group, and it is more efficient to consider these reports in one place. 

In 1993 Dixon and Jurs [209] used empirically calculated atomic charges to describe the pK s of a diverse collection of alcohols, phenols, and carboxylic acids. They found a strong linear relationship (r = 0.993) between their charge parameters and the pK s for a set of 135 oxyacids. Citra later used charges and bond orders from AMI calculations to characterize the pK s of phraiols, carboxylic acids, and alcohols [210]. Here too the best correlations were found for the phenols. Citra also compared his MLR results with results from two commercially available programs and found that all three approaches performed well. He cautioned, however, that his molecular orbital results were sensitive to the final optimized geometry found in the calculations. 

Chattaraj and co-workers [284] have used a group philicity index cOg to estimate the pK s of a variety of alcohols, phenols, and carboxylic acids This index derives from earlier work of Parr, Szentpaly, and Liu [240], Using the group philicity index for the COOH group in a set of carboxylic acids, for example, they obtained the relation... 

In 1959 Ballinger and Long [483] made a careful study of the dissociation constant of trifluoroethanol in HjO and D2O, and found Ka(H20) = 4.3 X 10 and Kj,(D20) = 0.95 x 10 , so that the respective pK s were 12.4 and 13.0. This turns out to be a rather typical result, at least for alcohols, where the acidity constant K, in H2O is ca. 3-5 times greater than that in D2O, and pK (H20) is roughly 0.6 pK units lower than pIL,(D20) Bunton and Shiner [484] concluded that the D2O effect was due to zero-point energy changes mainly associated with hydrogen bonds. In 1963 Bell and Kuhn [485] determined the pK, s of a number of alcohols, phenols, and carboxylic acids in H2O and D2O and obtained some evidence that ApK = pK (D20) - pK (H20) increased with pK (H20) for alcohols and phenols but no such evidence for carboxylic acids. 

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