Halogens, with alcohols

Aliphatic halides, and aromatic hydrocarbons with halogen in side-chain, are readily hydrolysed by boiling with alcoholic NaOH solution. 

This method is also used with alcohols of the stmcture Cl(CH2) OH (114). HaloaLkyl chlorosulfates are likewise obtained from the reaction of halogenated alkanes with sulfur trioxide or from the chlorination of cycHc sulfites (115,116). Chlorosilanes form chlorosulfate esters when treated with sulfur trioxide or chlorosulfuric acid (117). Another approach to halosulfates is based on the addition of chlorosulfuric or fluorosulfuric acid to alkenes in nonpolar solvents (118). 

Bromine is soluble in nonpolar solvents and in certain polar solvents such as alcohol and sulfuric acid. It is miscible with alcohol, ether, carbon disulfide, and many halogenated solvents. Bromine reacts with some of these solvents under certain conditions. 

In an analogous manner, DCPD reacts with alcohols and phenols to form ether derivatives, and with halogen acids, thiocyanic acid, and various carboxyhc acids to form esters. These esters are used as perfume components (67). Dicyclopentadiene alcohol and a number of the ethers, esters, and glycol adducts have been claimed as coal and ore flotation aids (68). 

One scheme for preparation of the diamine side chain consists in first reducing the carbonyl group of the haloketone, 73. Displacement of the halogen with diethylamine gives the amino alcohol (74). Treatment of that intermediate with thionyl bromide serves to replace the hydroxyl by bromine (75). The synthesis is completed by displacement of the bromine with ammonia. 

Thus, reduction of the Mannich reaction product (65) from acetophenone leads to alcohol 66. Replacement of the hydroxyl group by chlorine (67) followed by displacement of halogen with the anion from o-cresol affords the ether 68. Removal of one of the methyl groups on nitrogen by means of the von Braun reaction or its modem equivalent (reaction with alkyl chloroformate followed by saponification) leads to racemic 69 which is then resolved with L-(+)-mandelic acid to give the levorotary antidepressant tomoxetine (69) [16]. 

An ester of alanine with an arylaliphatic alcohol has shown promise as a non-tricyclic antidepressant. It may be speculated that the hindered milieu of the ester linkage protects the compound from hydrolysis by endogenous esterases. The preparation starts by reaction of pheny-lacctate 83 with methyl magnesium iodide to give tertiary carbinol 84. Acylation with 2-bromo-]>ropionyl bromide leads to ester 85 displacement of halogen with ammonia leads to alaproclate ( 6) [211. 

Janssen DB, J Gerritse, J Brackman, C Kalk, D Jager, B Witholt (1988) Purification and characterization of a bacterial dehalogenase with activity towards halogenated alkanes, alcohols and ethers. Eur J Biochem 171 67-72. 

The reaction is performed most simply by the addition of the propargylic alcohol to a solution of the phosphorus halide. Rearrangement of the phosphorus ester proceeds at ambient temperature or with mild heating. When phosphorus trihalides are used, the product can be isolated as the phosphonic dichloride.168169 Aqueous workup provides the phosphonic acid.162 In most instances, however, a dialkyl phosphorochloridite with only a single halogen on phosphorus available for reaction with alcohol has been used.165 170 174... 

Experiment.—Boil a few drops of benzyl chloride with (halogen-free) alcoholic potassium hydroxide solution for a few minutes in a test tube on the water bath. Then dilute with water, acidify with nitric acid, remove undissolved material by extraction with ether, and add a few drops of silver nitrate solution. 

When a haloalkane with p-hydrogen atom Is heated with alcoholic solution of potassium hydroxide, there Is elimination of hydrogen atom from p-carbon and a halogen atom from the a-carbon atom. As a result, an alkene is formed as a product. Since p-hydrogen atom is involved in elimination. It Is often called p-elimination. 

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