Reaction of Alcohols with Phosphorus Tribromide

The reaction of alcohols with phosphorus tribromide produces an alkyl halide plus phosphorous acid, which has a high boiling point and is water soluble. Therefore, the bromoalkane can be separated from the reaction mixture by distillation or by adding water. 

In the first step of this reaction, the nucleophihc oxygen atom of the alcohol displaces a bromide ion from the phosphorus tribromide to form the conjugate acid of a phosphite ester, ROPBr.  

Continued reaction, and successive displacement of bromide ion on the ROPBr intermediate, yields esters having the general formulas (ROj PBr and (ROj R These esters react with bromide ion to form the alkyl bromide product. For the sake of simphcity, we will only show the reaction of the ROPBr, intermediate. 

In the second step of the reaction, the C—O bond of the phosphite ester breaks, with predominant inversion of configuration. Some loss of optical activity and a smah amount of rearrangement may occur. For example, 2-bromobutane formed from opticahy active 2-butanol is about 80% optically pure. About 2% of the product is 2-bromo-2-methylpropane. 

The reaction of 3-pentanol with phosphorus tribromide yields a mixture of 3 bromopentane and 2-bromopentane in approximately a 9 1 ratio. Explain the source of each product. 

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Reaction of alcohols with phosphorus tribromide (Section 4 13) As an alternative to converting alco hols to alkyl bromides with hydrogen bromide the inorganic reagent phosphorus tribromide is some times used... 

Another general method for converting alcohols to halides involves reactions with halides of certain nonmetallic elements. Thionyl chloride, phosphorus trichloride, and phosphorus tribromide are the most common examples of this group of reagents. These reagents are suitable for alcohols that are neither acid sensitive nor prone to structural rearrangement. The reaction of alcohols with thionyl chloride initially results in the formation of a chlorosulfite ester. There are two mechanisms by which the chlorosulfite can be converted to a chloride. In aprotic nucleophilic solvents, such as dioxane, solvent participation can lead to overall retention of configuration.7... 

Exercise 15-21 Write the steps that could plausibly take place in the reaction of a primary alcohol with phosphorus tribromide in the presence of the weak base pyridine to give an alkyl bromide. 

S-methylhept3n-2-one (178) with methyl diethylphosphonoacetate (179) and sodium methoxide followed by reduction with LiAIH4 resulted In the alcohol 180. Treatment of 180 with phosphorus tribromide and triphenylphosphine gave the Cio-phosphonium salt 181. The Wittig reaction with apo-8 -lycopenal (182) and sodium methoxide gave rhodopin (177) in an overall yield of 20% referred to 178 (Scheme 42). 

The mechanism for the reaction of phosphorus tribromide with alcohols is similar to that for the reaction of alcohols with thionyl chloride. The alcohol reacts with PBr3 giving an intermediate of the type ROPBr2 which reacts with the nucleophilic bromide ion. 

It is necessary to use different procedures to prepare secondary alkyl bromides from secondary alcohols because such alcohols are easily dehydrated by concentrated sulfuric acid to give alkenes by way of Equations 14.13 and 14.14. In fact, the acid-catalyzed dehydration of secondary and tertiary alcohols is a common method for synthesizing alkenes (Sec. 10.3). This problem may be circumvented by using concentrated hydrobromic acid however, it is better to prepare secondary alkyl bromides by the reaction of secondary alcohols with phosphorus tribromide, PBrg (Eq. 14.16). 

Reaction of alcohols with thionyl chloride or phosphorus tribromide (15.3)... 

Tetrahydroimidazo[5,l-c][l,2,4]triazine 474 was prepared (79KGS1540) by treating imidazole derivatives 472 or 473 with hydrazine. Compound 473 was obtained by reaction of the respective imidazole with 1,2-dibromoethane or by the reaction of the alcohol derivative 471 with phosphorus tribromide. On the other hand, chlorination of471 with thionyl chloride gave 472 (Scheme 100). 

In a similar vein, the keto bridge in 5 can be replaced by oxygen with retention of activity. Reduction of acetophenone derivative 19 by means of sodium borohydride leads to the corresponding alcohol (20). Reaction with phosphorus tribromide with cyanide gives... 

The mechanism for the reactions with phosphorus halides can be illustrated using phosphorus tribromide. Initial reaction between the alcohol and phosphorus tribromide leads to a trialkyl phosphite ester by successive displacements of bromide. The reaction stops at this stage if it is run in the presence of an amine which neutralizes the hydrogen bromide that is formed.9 If the hydrogen bromide is not neutralized the phosphite ester is protonated and each alkyl group is successively converted to the halide by nucleophilic substitution by bromide ion. The driving force for cleavage of the C—O bond is the... 

Monosubstitution products of 3,5-dichloro-4-oxo-l,2,6-thiadiazine 235, in which a chlorine atom is replaced by reaction with, for instance, p-hydroxybenzyl alcohol, followed by treatment with phosphorus tribromide, are featured as fungicides in a patent (78USP4097594). 2,1,3-... 

Reactions with —OH Groups and Epoxides.—The formation of A -l,2-oxaphos-pholen derivatives from propargylic alcohols and phosphorus trichloride has been studied in detail. Intermediate phosphites (24) and allenic phosphonates (25) are described, and the A -l,2-oxaphosphoIen is produced in the final stage, as shown. Improved conditions have been outlined for the preparation of allylic bromides (26) from allylic alcohols and phosphorus tribromide. Related reactions of primary alcohols with the complex of phosphorus trichloride and DMF lead to the chloride (27) 22 addition of zinc bromide to the reaction results in the formation of alkyl bromides, but an attempt to extend this exchange to the preparation of cyanides was not successful. ... 

The 4-monosubstituted phosphabenzene (102) has been obtained from the corresponding 1,4-dihydrostannin by reaction with phosphorus tribromide. Phosphorins having one carbon- and one oxygen-linked substituent on phosphorus may be made directly by the reaction of phosphorins (103) with diazo-alkanes in the presence of alcohols or phenols. ... 

Many simple compounds of phosphorus are known, but they do not warrant detailed description here. Esters of phosphoric acid and phosphorous acid are formed when the halides of phosphorus are treated with an alcohol. It has already been pointed out that the interaction of these substances yields alkyl halides, a number of reactions taking place simultaneously. Typical reactions are those which take place between alcohol and phosphorus tribromide —... 

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