Bromides alkyl, from alcohols

A considerable amount of hydrobromic acid is consumed in the manufacture of inorganic bromides, as well as in the synthesis of alkyl bromides from alcohols. The acid can also be used to hydrobrominate olefins (qv). The addition can take place by an ionic mechanism, usually in a polar solvent, according to Markownikoff s rule to yield a secondary alkyl bromide. Under the influence of a free-radical catalyst, in aprotic, nonpolar solvents, dry hydrogen bromide reacts with an a-olefin to produce a primary alkyl bromide as the predominant product. Primary alkyl bromides are useful in synthesizing other compounds and are 40—60 times as reactive as the corresponding chlorides (6). 

DIMETHYL-3-PHENYLPRO-PIONALDEHYDE, 54, 46 Alkylboranes, oxidation, 52, 59 synthesis, 52, 59 Alkyl bromides, from alcohols, 54, 66... 

Alkyl bromides, from alcohols, benzyl bromide, and triphenyl phosphite,... 

Akylation, of acids, 50, 61 by oxonium salts, 51,144 Alkyl bromides, from alcohols, benzyl bromide, and triphenyl phosphite,... 

Hydrobromic acid is used in the preparation of inorganic bromide salts. The acid also is used for many organic syntheses, including alkyl bromides from alcohols or olefins, and bromophenols from phenols. The compound also is used as an acid catalyst in many alkylation, selective oxidation, isomerization, and dehydrogenation reactions. Other apphcations are in extraction of minerals and use as a reducing agent. 

The Mitsunobu reaction was discussed in Chapter 17, p. 000. Mitsunobu chemistry involves using a phosphorus atom to remove the OH group, after the style of PBrs as a reagent to make alkyl bromides from alcohols. 

Hydrogen bromide is used as a reagent and catalyst in several types of organic reactions such as the formation of alkyl bromides from alcohols. 

We have now learned two methods to prepare an alkyl chloride and two methods to prepare an alkyl bromide from an alcohol. If there is one good way to carry out a reaction, why search for more A particular reagent might work well for one starting material, but not so well for another. 

Direct substitution of F for OH by means of HF has no preparative importance. All the methods of preparing alkyl fluorides from alcohols proceed in principle by way of esters the alcohol is converted into the alkyl chloride, bromide, iodide, or / -toluenesulfonate, and then the halogen atom (see page 204) or the tosyloxy group (see page 229) is replaced by fluorine. 

The best method of preparing higher alkyl bromides (from C6) is to treat the alcohols with dry HBr 899-901... 

The synthesis of two alkyl halides from alcohols is the basis for these experiments. In the first experiment, a primary alkyl halide n-butyl bromide is prepared as... 

The mixture of hydrobromic acid and sulfuric acid may be prepared by either adding concentrated sulfuric acid to concentrated hydrobromic add or by generating the hydrobromic acid in situ by adding concentrated sulfuric acid to aqueous sodium bromide (Eq. 14.12). Both of these methods work well and give good yields of the alkyl bromide from low-molar-mass alcohols. The method of generating H-Br in situ is not effective with higher-molar-mass alcohols because of their low solubility in concentrated salt solutions, so concentrated (48%) hydrobromic acid is used instead. 

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). 

PROBLEM 7.48 Write a mechanism for the formation of alkyl bromides from the reaction of alcohols and PBrg. 

FIGURE 21.20 The mechanism for formation of an alkyl bromide from a primary or secondary alcohol and hydrogen bromide. 

Alkyl Bromides from Aleohols. Alkyl bromides (29) are obtained in high yields by the reaction of the corresponding alcohols (28) with Me6Si2 and p)nidinium hydrobromide perbromide (eq 14). The substitution reaction is very fast for tertiary, allylic, and benzylic alcohols, but very slow for primary and secondary alcohols. Inversion of configuration is observed with secondary alcohols. 

We know that we can synthesize an alkyl bromide from an alcohol with PBt3. 

The reaction of alkyl bromides with alcohols to form ethers, promoted by silver salts of dicarboxylic acids, the Koenigs-Knorr synthesis, is sometimes complicated by the recovery of the ether from the dicarboxylic acid. A copolymer network of maleic acid and l,4-bis(vinyloxy)butane was transformed into the silver salt (41) and used for the reaction of 2,3,4,6-tetra-O-acetyl-la-bromoglucopyranose with cholesterol to give the cholesteryl ether in 55% yield as shown in Scheme The polymeric by-product dicarboxylic acid was filtered easily from the product solution. 

Introduction. The Ph3PBr2 adduct was first used in synthesis in 1959 for the preparation of alkyl and acyl bromides from alcohols and carboxylic acids, and for the dehydration of amides and oximes to nitriles. Since then it has been widely employed as a versatile reagent for a number of synthetic reactions. 

Mix 40 g. (51 ml.) of isopropyl alcohol with 460 g. (310 ml.) of constant boiling point hydrobromic acid in a 500 ml. distilling flask, attach a double surface (or long Liebig) condenser and distil slowly (1-2 drops per second) until about half of the liquid has passed over. Separate the lower alkyl bromide layer (70 g.), and redistil the aqueous layer when a further 7 g. of the crude bromide will be obtained (1). Shake the crude bromide in a separatory funnel successively with an equal volume of concentrated hydrochloric acid (2), water, 5 per cent, sodium bicarbonate solution, and water, and dry with anhydrous calcium chloride. Distil from a 100 ml. flask the isopropyl bromide passes over constantly at 59°. The yield is 66 g. 

Place a mixture of 0-5 g. of finely powdered thiourea, 0-5 g. of the alkyl halide and 5 ml. of alcohol in a test-tube or small flask equipped with a reflux condenser. Reflux the mixture for a j)eriod depending upon the nature of the halide primary alkyl bromides and iodides, 10-20 minutes (according to the molecular weight) secondary alkyl bromides or iodides, 2-3 hours alkyl chlorides, 3-5 hours polymethy lene dibromides or di-iodides, 20-50 minutes. Then add 0 5 g. of picric acid, boil until a clear solution is obtained, and cool. If no precipitate is obtained, add a few drops of water. RecrystaUise the resulting S-alkyl-iso-thiuronium picrate from alcohol. 

The synthesis of these disubstituied thioureas takes place in three steps. First the alkyl bromide is prepared by the action of hydrobromic acid on the corresponding alcohol (518). Then the dialkylcyanamide is obtained by treatment at 25°C with calcium cyanamide. The yields are of the order of 30 to 60%. Thioureas are obtained in a third step from the cyanamide by reaction at 40 C with HjS in the presence of pyridine. Yields ranged from 57 to 90% (518),... 

Additional evidence for carbocation intermediates in certain nucleophilic substitutions comes from observing rearrangements of the kind normally associated with such species For example hydrolysis of the secondary alkyl bromide 2 bromo 3 methylbutane yields the rearranged tertiary alcohol 2 methyl 2 butanol as the only substitution product... 

Both reactants m the Williamson ether synthesis usually originate m alcohol pre cursors Sodium and potassium alkoxides are prepared by reaction of an alcohol with the appropriate metal and alkyl halides are most commonly made from alcohols by reaction with a hydrogen halide (Section 4 7) thionyl chloride (Section 4 13) or phosphorus tri bromide (Section 4 13) Alternatively alkyl p toluenesulfonates may be used m place of alkyl halides alkyl p toluenesulfonates are also prepared from alcohols as their imme diate precursors (Section 8 14)... 

Triphenyl phosphine dibromide [1034-39-5] M 422.1, m 23.5 , 245-255 (dec). Recrystd from MeCN-Et20. Although it has been recrystd from EtOH, this is not recommended as it converts alcohols to alkyl bromides. It deteriorates on keeping and it is best to prepare it afresh. [Anderson and Freenor J Am Chem Soc 86 5037 1964 Homer et al. Justus Liebigs Ann Chem 626 26 1959.]... 

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