Alcohols with phosphorus tribromide

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... 

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. 

A concise synthesis of the methobromide of ungeremine (45) featured the oxidative photocyclization of the Schiff base 43 to provide 44 (Scheme 2). When 44 was reduced with LiAlH4 followed by treatment of the resulting alcohol with phosphorus tribromide, an alkyl bromide was generated that suffered spontaneous cyclization to furnish 45 (106). 

In a similar fashion, the treatment of a 1° or 2° alcohol with phosphorus tribromide, PBr3, forms an alkyl bromide. 

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). 

The reaction of an alcohol with phosphorus tribromide produces phosphorous acid, which has a high boiling point, and is water soluble. Therefore, the bromoaUtane can be separated from the reaction mixture by distillation or by adding water to dissolve the phosphorous acid and then extracting the hahde with ether. 

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... 

Reaction with phosphorus trihalides Alcohols are converted to alkyl bromides by reaction with phosphorus tribromide (Refer Unit 10, Class XII). 

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... 

The hydroxyl group of the side-chain alcohols is readily replaced by halogen by treatment with thionyl chloride 87,190,336,486,526-528,529 or by treatment with phosphorus tribromide in chloroform193 439 447-... 

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-... 

Alternatively, the alcohol could be treated with hydrogen bromide or with phosphorus tribromide to give the benzylic bromide and the bromide then allowed to react with sodium methoxide. 

The synthesis of bufotenine itself followed closely upon the proof of its structure. Hoshino and Shimodaira reduced the ethyl ester of 5-ethoxy-indole-3-acetic acid by the Bouveault-Blanc procedure to the corresponding primary alcohol, which was treated with phosphorus tribromide and then dimethylamine, to give the ethyl ether of bufotenine, which was demethylated with aluminum chloride (130). In a later synthesis, 2,5-dimethoxybenzyl cyanide (XXIII) was alkylated by Eisleb s method with dimethylaminoethyl chloride in the presence of sodamide to give l-(2,5-dimethoxyphenyl)-3-dimethylaminopropyl cyanide (XXIV), which was then hydrogenated over Haney nickel to yield 2-(2,5-di-methoxyphenyl)-4-dimethylaminobutylamine (XXV R = Me). De-methylation of this with hydrobromic acid, followed by oxidation of the product (XXV R = H) with potassium ferricyanide yielded bufotenine (XIX) via the related quinone (109). 

The allylic secondary alcohol l,5-hexadiene-3-ol reacts with phosphorus tribromide plus 2 drops of 48% hydrobromic acid to give in high yield a mixture of... 

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. ... 

A compound somewhat related to 902, the alcohol 905, has been isolated from peppermint and synthesized from 2,6-dimethyl-5,7-octadien-2-ol (called ocimenol by the authors). The action of peracetic acid on the latter gave the furan 906, and allylic rearrangement with phosphorus tribromide followed by replacement of the bromide with potassium acetate gave the ( ) + (Z) acetates of 905. ... 

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. ... 

Attempts to brominate the acetylenic alcohol (86) with phosphorus tribromide give low yields of either 2-bromo-3,5-di-t-butyl-l,2-oxa-A3-phospholen-2-oxide (87) or the allene (88), depending on the availability of protons... 

Heating the chloroacetyl compound 67 under reflux in ethanol yields the 3-0X0 compound 68. This was not isolated as such but was hydrogenated over platinum to give the perhydro compound 69. ° The 1-oxo compound 71 has similarly been prepared by treatment of the alcohol 70 with phosphorus tribromide or thionyl chloride and base.. ... 

In this synthesis famesyl bromide (156) was converted, with 2-nitropropane and KOH, into famesal (157). Homer-Emmons reaction with the Cs-phosphonate 73 and reduction with UAIH4 gave the alcohol 158 (32% yield referred to 156) which was transformed, with phosphorus tribromide and triphenylphosphine, to the C2o-phosphonium salt 159 (Scheme 35). 

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). 

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