Alkyl chlorides from alcohols

Phosphorus pentachloride is one of the most powerful reagents by which the hydroxyl of organic compounds can he replaced by chlorine. Alkyl chlorides, RC1, from alcohols, and acid chlorides, RCOC1, from acids, are often prepared by this method. The pentachloride is thereby converted first into the oxychloride, P0C13, which may itself be used for the substitution of OH by Cl. 

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. 

Section 8 14 Nucleophilic substitution can occur with leaving groups other than halide Alkyl p toluenesulfonates (tosylates) which are prepared from alcohols by reaction with p toulenesulfonyl chloride are often used... 

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)... 

The reactions of thionyl chloride with organic compounds having hydroxyl groups are important. Alkyl chlorides, alkyl sulfites, or alkyl chlorosulfites form from its reaction with aUphatic alcohols, depending on reaction conditions, stoichiometry, and the alcohol stmcture ... 

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). 

Formation of Ethers. Very high ether yields can be obtained from alcohols and phenols with dialkyl sulfates in CH2CI2 and concentrated NaOH—tetrabutylammonium chloride at room temperature or slightly elevated temperature within 1—5 h (18). Using excess aqueous caustic—N(C4H2)4HS04, unsymmetrical aUphatic ethers can be prepared with alkyl chlorides at 25—70°C in 3—4 h (19) (see Ethers). 

Alkyl chlorides from alcohols and chlo-rovinylamines, 41, 23 5 - A1 k y 1 -1,2,3,4,5-p c n tachlorocy clopcn -tadienes from hexachlorocydo-pentadiene and trialkyl phosphites, 43, 90 AlleNE, 43,12... 

Alkyl chlorides, from alcohols, benzyl chloride, and triphenyl phosphite,... 

Alcohols react with sulphonyl chlorides to yield sulphonate esters via Sn2 reaetions. Tosylate esters (alkyl tosylates) are formed from alcohols from the reaetion with p-toluenesulphonyl ehloride (TsCl). The reaction is most commonly carried out in the presenee of a base, e.g. pyridine or triethyla-mine (Et3N). 

Although detailed mechanisms have not been established, the first step is thought to be formation of an unstable mixed anhydride, which then extrudes S02 and collapses with attack of chloride at the carbonyl carbon. A similar mechanism occurs in the formation of alkyl chlorides from alcohols and thionyl chloride (Section 15-5A) ... 

Reaction XLIII. (a) Formation of Esters by the action of Acid Anhydrides or of Acid Chlorides on an Alcohol in the presence of Magnesium Alkyl Halide (Grignard). (B., 39, 1738.)—This application of the Grig-nard reaction to the preparation of esters is of theoretical rather than practical interest as illustrating the wide applicability of this many-sided reaction. The steps in the synthesis will be clear from the examples given they are somewhat different from the usual phases of a Grignard reaction. 

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