Hydrobromic acid reactions with alcohol

A given alcohol is treated with 25 percent excess of aqueous (48 per cent) hydrobromic acid together with sulfuric acid. The mixture is refluxed in order to convert the alcohol as completely as possible into the corresponding bromide, and the latter is then removed from the reaction mixture by distillation. Slight variations from this procedure depend upon the physical and chemical properties of the alcohol used, or of the bromide formed in the reaction. For example, in the preparations of ethyl and allyl bromides, the reaction mixture is not refluxed because of the volatility of the former compound, and because of the chemical reactivity of the latter in the preparation of wo amyl bromide, too large a proportion of sulfuric acid may produce appreciable decomposition while halides of high molecular weight, because of their low volatility, are separated from the reaction mixture mechanically, instead of by distillation. 

By treatment of the alcohol with a mixture of constant boiling point hydrobromic acid and concentrated sulphuric acid the presence of sulphuric acid results, as a rule, in more rapid reaction and improved 3delds. A typical example is ... 

A) Sn2 substitution at the allylic alcohol with hydrobromic acid followed by reaction with the requisite secondary amine, or... 

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),... 

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. 

Hydrogen bromide adds to acetylene to form vinyl bromide or ethyHdene bromide, depending on stoichiometry. The acid cleaves acycHc and cycHc ethers. It adds to the cyclopropane group by ring-opening. Additions to quinones afford bromohydroquinones. Hydrobromic acid and aldehydes can be used to introduce bromoalkyl groups into various molecules. For example, reaction with formaldehyde and an alcohol produces a bromomethyl ether. Bromomethylation of aromatic nuclei can be carried out with formaldehyde and hydrobromic acid (6). 

B. a-Hydroxyphenazine (demethylalion). A solution of 4.2 g. (0.02 mole) of a-methoxyphenazine, from A above, in 125 ml. of 55% hydrobromic acid (Note 7) is placed in a 250-ml. round-bottomed flask fitted with a reflux condenser. The flask is immersed in an oil bath, and the solution is heated to 110-120° for 5 hours the evolved gases are absorbed with water in a trap. The reaction mixture is cooled to room temperature, diluted with about 125 ml. of water, almost neutralized with sodium hydro.xide (Note 8), and extracted six times with 30- to 40-ml. portions of ether. The combined ether extracts arc extracted with 25-ml. portions of 10% sodium hydroxide solution (Note 9) until no more purple sodium salt is remox ed from the ether. The aqueous extracts are combined, made acid to litmus with dilute acetic acid, and re-extracted four times with 50-ml. portions of ether. The combined ether extracts are dried over anhydrous sodium sulfate, and the ether is removed by distillation on a steam bath. The residue is recrystallized as follows It is dissolved in the least possible amount of hot alcohol, water... 

One common kind of reaction involves proton transfer occurring as a rapid equilibrium preceding the rate-determining step, for example, in the reaction of an alcohol with hydrobromic acid to give an alkyl bromide ... 

This synthesis came shortly after one by Prelog, Kohlberg, Cerkovnikov, Rezek and Piantanida (1937) based on a series of reactions which, with modifications and extensions. Prelog and his colleagues have applied to the syntheses of bridged heterocyclic nuclei, of which this is an example. 4-Hydroxymethyltetrahydropyran (VI R =. OH) is converted via the bromo-compound (VI R = Br) and the nitrile (VI R = CN) into tetrahydropyran-4-acetic acid of which the ethyl ester (VII) is reduced to 4-()3-hydroxyethyl)-tetrahydropyTan (VIII). This is converted by fuming hydrobromic acid into 3-(2-bromoethyl)-l 5-dibromopentane (IX) which with ammonia in methyl alcohol yields quinuclidine (V). 

The prominent role of alkyl halides in formation of carbon-carbon bonds by nucleophilic substitution was evident in Chapter 1. The most common precursors for alkyl halides are the corresponding alcohols, and a variety of procedures have been developed for this transformation. The choice of an appropriate reagent is usually dictated by the sensitivity of the alcohol and any other functional groups present in the molecule. Unsubstituted primary alcohols can be converted to bromides with hot concentrated hydrobromic acid.4 Alkyl chlorides can be prepared by reaction of primary alcohols with hydrochloric acid-zinc chloride.5 These reactions proceed by an SN2 mechanism, and elimination and rearrangements are not a problem for primary alcohols. Reactions with tertiary alcohols proceed by an SN1 mechanism so these reactions are preparatively useful only when the carbocation intermediate is unlikely to give rise to rearranged product.6 Because of the harsh conditions, these procedures are only applicable to very acid-stable molecules. 

Preparation of Allenes by the Reaction of Acetylenic Alcohols with Hydrobromic Acid-Cuprous Bromide [73a]... 

Alkyl Bromides General Discussion. When an alcohol is heated with aqueous 48 per cent hydrobromic acid, a partial conversion takes place into the corresponding bromide. The reaction is, however, more rapid and more complete in the presence of sulfuric acid. Although the constant boiling hydrobromic acid obtainable on the market may be used in all the above experiments, its preparation by the sulfur-dioxide reduction of bromine will be considerably cheaper and equally convenient, provided a cylinder of sulfur dioxide is available. For use in the preparation of alkyl bromides, distillation of the bromine-sulfur dioxide reduction mixture is superfluous. 

In a 5-I. flask fitted with a downward condenser, are placed 340 g. of methylene aminoacetonitrile (p. 47) and 2500 g. of 48 per cent hydrobromic acid (Note 1). The mixture is heated on the steam bath for three hours (Note 2). The pressure in the apparatus is then reduced and dilute acid and formaldehyde are distilled into a water-cooled receiver until the separation of ammonium bromide from the reaction mixture causes bumping. This occurs when approximately half of the liquid has been distilled over. The ammonium bromide is filtered from the hot liquid and washed with a small amount of cold water the filtrates are returned to the flask and distillation continued as nearly as possible to dryness (Note 3). The residue is dissolved in 2 1. of cold methyl alcohol and filtered to the filtrate is added 350 cc. of pyridine, with vigorous shaking (Note 4). 

The benzylbromomalonic acid containing water is now heated in an oil bath to 125°—130°, and the fused mass evolves carbon dioxide and a certain amount of hydrobromic acid. The reaction is complete in the course of 30—45 minutes. The residue is a yellow oil, which even at a low temperature does not crystallise, and which in the main consists of phenyl-a-bromopropionic acid. For the purpose of purification it is washed with water, taken up in ether, and dried with anhydrous sodium sulphate the ether is then distilled off. The mobile, almost colourless oil remaining is dissolved in 5 times its volume (excess) of 25% aqueous ammonia, and either heated for 3 hours to 100° in a sealed tube or allowed to stand for 3 to 4 days at ordinary temperature. On evaporation of the ammo-niacal solution an almost colourless residue is left, and this chiefly consists of ammonium bromide and phenylalanine. On boiling with absolute alcohol the amino-acid is left undissolved and is recrystallised from hot water. 

Add 8.0g (10.0ml, 0.15 mol) of redistilled acrylonitrile (Expt 5.161, Note (1)) to a stirred solution of diethyl propylmalonate (30.2 g, 0.15 mol) (Expt 5.132) and of 30 per cent methanolic potassium hydroxide (4.0 g) in t-butyl alcohol (100 g). Keep the reaction mixture at 30-35 °C during the addition and stir for a further 3 hours. Neutralise the solution with 2 M-hydrochloric acid, dilute with water and extract with ether. Dry the ethereal extract with anhydrous sojdium sulphate and distil off the ether the residue [diethyl (2-cyanoethyl)-propylmalonate 11 g] solidifies on cooling in ice, and melts at 31—32 °C after recrystallisation from ice-cold ethanol. Boil the cyanoethyl ester (10 g) under reflux with 40 ml of 48 per cent hydrobromic acid solution for 8 hours, and evaporate the solution almost to dryness under reduced pressure. Add sufficient water to dissolve the ammonium bromide, extract several times with ether, dry the ethereal extract and distil off the solvent. The residual oil (4.5 g, 66%) soon solidifies upon recrystallisation from water, pure 2-propylglutaric acid, m.p. 70 °C, is obtained. 

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