Tertiary alcohols reaction with halogen acids

Acid halides are among the most reactive of carboxylic acid derivatives and can be converted into many other kinds of compounds by nucleophilic acyl substitution mechanisms. The halogen can be replaced by -OH to yield an acid, by —OCOR to yield an anhydride, by -OR to yield an ester, or by -NH2 to yield an amide. In addition, the reduction of an acid halide yields a primary alcohol, and reaction with a Grignard reagent yields a tertiary alcohol. Although the reactions we ll be discussing in this section are illustrated only for acid chlorides, similar processes take place with other acid halides. 

Before the synthesis of the pseudoureas was published, Bernthsen and Klinger [6] reported a pseudothiourea synthesis involving the reaction of thioureas with alkyl halides. This reaction was briefly reviewed by Dains [16] and Stieglitz [49, 50], and it found many commercial applications [51-53]. The preparation of isothiouronium salts by the direct action of thiourea and halogen acids on alcohols (primary, secondary, and tertiary) was reported by Stevens [8] and further developed by Johnson and Sprague [54, 55] (Eq. 25). 

The reaction reaches equilibrium rapidly if the hydroxyl group is attached to a reactive radical, as in tertiary alcohols. In such cases, excess of the halogen acid is shaken with the alcohol, and the mono-halogen compound is separated. With primary and secondary alcohols, equilibrium is reached more slowly, and a catalyst (such as zinc chloride in the case of hydrochloric acid, and sulfuric acid in the case of hydrobromic acid) is used. On account of its cost, hy-driodic acid is not used, but iodine and phosphorus, which react as follows ... 

This reaction is obviously only of importance when the halogen alkyl is not obtained from the corresponding alcohol, as is the case in the example given. As above mentioned, the isopropyl iodide is most simply obtained from glycerol and hydriodic acid, so that by this reaction the glycerol can be converted into the isopropyl alcohol (compare Reaction 13). Halogen alkyls also unite directly with other compounds, like sulphides and tertiary animes ... 

Functionalized benzylic mesylates containing a halogen atom were also investigated. Reactions of the halogenated benzyl manganese mesylates with acid chlorides, aldehydes, and ketones yielded the corresponding ketone, secondary alcohol, and tertiary alcohol in good to excellent isolated yields as shown in Table 8.11. As mentioned earlier, it is of interest that the mesylates... 

The use of palladium and ruthenium as halogen-free carbonylation catalysts has been studied intensively by Shell. The catalysts were principally designed for the carbonylation of olefins in the presence of alcohols in order to yield carboxylic esters [26], but work also well for the synthesis of carboxylic acids or anhydrides. The latter are formed when the reaction is conducted in an acid as a solvent [27]. The palladium systems typically consist of palladium acetate, tertiary phosphines, and strong acids such as mineral acids or acids with weak or noncoordinating anions such as p-toluenesulfonic acid. Remarkable activities are achieved when aromatic phosphines that carry pyridines as substituents are... 

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