Alcohol in acid

The ether forms spontaneously from the tertiary alcohols in acid. 

Various quantitative methods have been developed to express the relative stabilities of carbocations. One of the most common of these, though useful only for relatively stable cations that are formed by ionization of alcohols in acidic solutions, is based on the equation ... 

Table 7.2 Solubility of Some Alcohols in Acid Solution...

This beneficial effect of fluorination on hydrolytic stability has also been demonstrated with the synthetic prostaglandin SC-46275 (Fig. 70). This compound possesses an anti-secretory activity that protects the stomach mucous membrane. However, its clinical development was too problematic because of the instability of the tertiary allyl alcohol in acidic medium (epimerisation, dehydration, etc.). A fluorine atom was introduced on the C-16 methyl to disfavour the formation of the allylic carbocation. This fluorinated analogue possesses the same biological activity, but does not undergo any degradation or rearrangement, and itepimerises only slowly [165]. 

As described in the section dealing with liquid chromatographic methods, the reaction of 0,0-di-substituted tartaric anhydrides with racemic amino alcohols in acidic solution leads exclusively to the corresponding diastereomeric monoesters, which are easily separated by reversed-phase HPLC. However, H- and sometimes 13C-NMR spectra of these compounds are in many cases also highly useful for determining the diastereomeric ratio and in many cases the absolute configuration. 

The chemistry in this area (6-8) has been approached from two different directions reduction of Cr(VI) or oxidation of Cr(II) it is only recently that an overall, self-consistent picture has emerged (7,9). The key experiment is the observation that the reaction between Cr(VI) and alcohols in acid solution under an 02 atmosphere yields [(H20)5 Cijii02]2+, a Cr(III) superoxo complex,1 according to the sequence (1). 

Most liquid chromatographic experiments performed with PAD employ alkaline mobile phases or use postcolumn addition of base to get the electrode at the appropriate pH for the formation of the oxide. The exceptions to this are the detection of carbohydrates and alcohols in acidic media and the detection of sulfur compounds. The oxidation of carbohydrates and alcohols is not oxide catalyzed, and since they exhibit a stronger adsorption to piatinum than gold, they can be determined under acidic conditions. Sulfur compounds are adsorbed at oxide-free surfaces, and the kinetics for detection are favorable even at pH values below 7. 

Equilibria other than proton transfer have also been used to determine acidity functions. One of these is based on the ionization of alcohols (mainly arylmethyl alcohols) in acid solution following the equilibrium in Eq. (1.17). 

If on the other hand the Sn2 reaction with cyanide is favoured, as with allylic 47 or benzylic 50 halides, that method is better.15 Hydrolysis of the nitrile 48 gives the acid 49 but treatment with an alcohol in acidic solution gives the ester 52 directly.16... 

Compared to simple alkyl cations, triarylmethyl cations are well characterized in terms of structure and stability, and react with a number of readily oxidized species including aliphatic amines (El tsov et al., 1978) and ethers (Kabir-ud-Din and Plesch, 1978). Their reduction by alcohols in acidic medium have an historic importance in the area (Bartlett and McCollum, 1956), and the use of triarylmethanes as hydride carriers is an area of continuing interest (Ivanov et al., 1982). 

This is not, of course, the end of the reaction as R+ is very reactive and we shall see the sort of things it can do in Chapters 17 and 19. More commonly, some sort of catalysis is involved in decomposition reactions. An important example is the decomposition of tertiary alcohols in acid solution. The carbon-oxygen bond of the alcohol does not break by itself but, after the oxygen atom has been protonated by the acid, decomposition occurs. 

A similar reaction occurs when enol ethers react with alcohols in acid solution and in the absence of water, but now we are starting in the middle of the acetal hydrolysis mechanism and going the other way, in the direction of the acetal A useful example is the formation of THP (= TetraHydroPyranyl) derivatives of alcohols from the enol ether dihydropyran. You will see THP derivatives of alcohols being used as protecting groups in Chapter 24. 

Rearrangement of this tertiary alcohol in acid gives the target natural product. The four-membered ring has certainly disappeared but it may not be obvious at first what has taken its place. 

A few percent of the was a product similar chromatographi-cally to the parent surfactant, WPh 6E0. Its EI-MS, however, had no 399 tropylium ion an intense m/ 411 suggested that another alkyl substituent was present (Figure 3). This was interpreted as the result of a rearranged carboniiun ion (14) from the 2° alcohol in acidic media (10). Mild acidic hydrolysis (aqueous HCl in CHqOH) successfully released the 2 alcohol from the major HPLC peak C-2. 

Oxidation of primary alcohols in acid media is often accompanied by esterification. By the use of the proper proportions of reactants, fair yields of esters may be obtained directly from the alcohols e.g., -butyl n>butyrate (47%) by chromic acid oxidation of n-butyl alcohol. Aqueous acid chlorate solutions in the presence of vanadium pentoxide have been used for this purpose. ... 

The preceding arsinic acid (5 grams), in 50 c.c. of water and 10 c.c. of concentrated hydrochloric acid, is reduced with 7 to 10 grams of sodium hypophosphite and 8 c.c. of a one per cent, solution of potassium iodide by warming the mixture on the water-batli and passing in a stream of carbon dioxide. The reduction product separates, is filtered off,washed with dilute hydrochloric acid, and dried at 50° C. in a vacuum. The yield is 80 per cent. The arseno-compound is a yellowish-red, amorphous powder, soluble in water and in small quantities in methyl alcohol, from which it may be precipitated by absolute alcohol. In acids and alkalis it is insoluble. 

The mechanisms of most alcohol reductions are obscure. Hydrogenolysis of benzyl alcohols can give inversion or retention of configuration, depending on the catalyst. The mechanism of electroreduction of allylic alcohols in acidic aqueous media has been examined. 

---