Primary alcohols reaction with halogen acids

Other Reactions. Primary amyl alcohols can be halogenated to the corresponding chlorides by reaction with hydrogen chloride in hexamethylphosphoramide (87). Neopentyl chloride [753-89-9] is formed without contamination by rearrangement products. A convenient method for preparing / f/-amyl bromide and iodide involves reaction of / f/-amyl alcohol with hydrobromic or hydroiodic acid in the presence of Li or Ca haUde (88). The metal haUdes increase the yields (85 —95%) and product purity. 

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). 

Protonation of the alcohol can be accomplished by using the halogen acids, HC1, HBr, and HI, which also provide the nucleophile for the reaction. These reaction conditions favor the SN1 mechanism, although primary alcohols still follow the SN2 path unless a resonance-stabilized carbocation can be formed. The acids HBr and HI work with most alcohols, but HC1, a weaker acid, requires the presence of ZnCl2 (a Lewis acid) as a catalyst when the alcohol is primary or secondary. Examples are shown in the following equations ... 

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 ... 

The bromides and iodides are conveniently prepared by distilling an alcohol with an excess of an aqueous solution of hydrobromic acid and hydriodic acid. The chlorides which contain primary alkyl groups cannot be made in this way. The reactions of the alcohols with aqueous solutions of the halogen acids have been described (55, 74). 

When halogen atoms are present in the epoxide such as in epichlorohydrin, 3,3,3-trichloropropylene oxide (TCPO) or 4,4,4-trichloro-l,2-butylene oxide (TCBO), or in the initiator, acid catalysts, e.g. boron trifluor-ide etherate, may be used (13-18). Vogt cind Davis (16) found that, if the concentration of catalyst/ini-tiator (polyol) complex is decreased with respect to TCPO in order to obtain higher molecular weight products, side reactions such as cyclization reactions become increasingly important. Boron trifluoride also promotes dimerization of alkylene oxides to dioxane or alkyl derivatives of dioxane as described by Fife and Roberts ( ). The use of acid catalysts, e.g. Lewis acids, promotes formation of a greater amount of terminal primary alcohol groups when compared to base catalysis of epoxides. 

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