Alcohol phosphorus halides, reactions

Another general method for converting alcohols to halides involves reactions with halides of certain nonmetallic elements. Thionyl chloride, phosphorus trichloride, and phosphorus tribromide are the most common examples of this group of reagents. These reagents are suitable for alcohols that are neither acid sensitive nor prone to structural rearrangement. The reaction of alcohols with thionyl chloride initially results in the formation of a chlorosulfite ester. There are two mechanisms by which the chlorosulfite can be converted to a chloride. In aprotic nucleophilic solvents, such as dioxane, solvent participation can lead to overall retention of configuration.7... 

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... 

The second reaction proceeds much more energetically than the first, especially if preformed phosphorus halide is used. This is, however, not always necessary, at least not in the case of replacements by bromine and iodine in many cases the procedure is rather to produce the halide only during the reaction, either by dropping bromine from a separating funnel into a mixture of alcohol and red phosphorus or, as above, by adding finely powdered iodine. Like the former, this reaction can also be applied to polyhydric and to substituted alcohols indeed, it is possible to replace all the OH groups by halogens, and in particular also by chlorine. 

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... 

Alkyl halides are almost always prepared from corresponding alcohols by the use of hydrogen halides (HX) or phosphorus halides (PX3) in ether (see Section 5.5.3). Alkyl chlorides are also obtained by the reaction of alcohols with thionyl chloride (SOCI2) in triethylamine (Et3N) or pyridine (see Section 5.5.3). 

Phosphorus halides react with alcohols to yield alkyl halides at low temperature (0 °C). Primary and secondary alcohols undergo Sn2 reactions with PX3. This type of reaction does not lead to rearranged products, and does not work well with 3° alcohols. PI3 has to be generated in situ via reaction of iodine and phosphorus. 

Propargyl alcohols may be converted to allenes by several methods, for example, (a) through the intermediate formation of propargyl halides which are not isolated but react directly with cuprous salts and hydrogen halide [60, 72-73] or cyanide [71] (b) typical alcohol reactions with thionyl chloride [74a-d] phosphorus halides [75-77], and miscellaneous reagents (see Scheme 3). 

Aliphatic alcohols do not undergo solvolysis as readily as benzylic alcohols, and are generally converted into halides under basic reaction conditions via an intermediate sulfonate. Because of the hydrophobicity of polystyrene, however, nucleophilic substitutions with halides on this support do not always proceed as readily as in solution (Table 6.3). Alternatively, phosphorus-based reagents can also be used to convert aliphatic alcohols into halides. 

Replacement of the hydroxyl group in a phenol by halogen cannot be accomplished by reaction with the hydrogen halides as in the case of alcohols, and reaction with phosphorus halides gives only low yields of halogenobenzenes (except in the case of nitrophenols), the main product being a phosphite or phosphate ester. 

Alcohols and phenols are also weak bases. They can be protonated on the oxygen by strong acids. This reaction is the first step in the acid-catalyzed dehydration of alcohols to alkenes and in the conversion of alcohols to alkyl halides by reaction with hydrogen halides. Alkyl halides can also be prepared from alcohols to alkyl halides by reaction with hydrogen halides. Alkyl halides can also be prepared from alcohols by reaction with thionyl chloride or phosphorus halides. 

Ethane occurs in natural gas, from which it is isolated. Ethane is among the chemically less reactive organic substances. However, ethane reacts with chlorine and bromine to form substitution compounds. Ethyl iodide, bromide, or chlorides are preferably made by reaction with ethyl alcohol and the appropriate phosphorus halide. Important ethane derivatives, by successive oxidation, are ethyl alcohol, acetaldehyde, and acetic acid. Ethane can also be used for the production of aromatics by pyrolysis (Fig. 1). 

Reactions of Alcohols with Phosphorus Halides 484 Reactions of Alcohols with Thionyl Chloride 485 11-9 Mechanism 11-3 Reaction of Alcohols with PBr3 485 11-10 Dehydration Reactions of Alcohols 487... 

Mechanism of the Reaction with Phosphorus Trihalides The mechanism of the reaction of alcohols with phosphorus trihalides explains why rearrangements are uncommon and why phosphorus halides work poorly with tertiary alcohols. The mechanism is shown here using PBr3 as the reagent PC13 and PI3 (generated from phosphorus and iodine) react in a similar manner. 

Phosphites can be very easily prepared by the reaction of a phosphorus halide with alcohol and an organic base, typically triethylamine or pyridine.36 It is generally necessary to use low temperatures and to keep the reaction free from moisture and air. If diols are used, reaction conditions can be adjusted so that oxygen either... 

The reaction between alcohol and phosphorus halide may proceed in another direction ... 

The replacement of an alcoholic hydroxyl group by a halogen atom is one of the most common reactions carried out in organic chemistry. The usual reagents for effecting the transformation include halogen acids, thionyl chloride, and phosphorus halides. The reaction is of particular theoretical interest since experiments with optically active alcohols suggest still another substitution process. It has been called an internal nucleophilic substitution reaction (S i).20... 

The second reaction takes place much more energetically, espe-dally when a phosphorus halide which has been previously made is used. This is not always necessary, at least in introdudng bromine and iodine in many cases it is better to generate the phosphorus halides in the course of the reaction, by adding to the mixture of alcohol and red phosphorus either bromine from a dropping funnel, or as above, finely pulverised iodine. This reaction, as well as the first, is applicable to poly-add alcohols and substituted alcohols, e.g. ... 

HX, SOX2, and phosphorus halides cause Walden inversion of optically active alcohols that have the OH group at a center of chirality. The inversion may be more or less complete according to the reaction conditions, so that the rotation of the halide obtained is liable to vary from one occasion to the next. For the steric course of replacement of OH by Br in steroids see Fieser.556... 

Primary, secondary, and tertiary alcohols undergo nucleophilic substitution reactions with HI, HBr, and HCl to form alkyl halides. These are Sn2 reactions in the case of primary alcohols and SnI reactions in the case of secondary and tertiary alcohols. An alcohol can also be converted into an alkyl halide by phosphorus trihalides or thionyl chloride. These reagents convert the alcohol into an intermediate with a leaving group that is readily displaced by a halide ion. 

Phosphorus pentachloride is employed as an esterification agent in the treatment of alcohols, the halide becoming hydrolyzed during the reaction. 

The hydroxyl group in alcohol can be replaced by a halogen atom by means of the halides of phosphorus. A reaction between alcohol and phosphorus trichloride takes place according to the equation,... 

The method of replacing a hydroxyl group by a halogen atom which is most general in its application, is that in which the compound containing this group is treated with a halide of phosphorus. These reactions have also been described (64). It should be noted that reactions take place other than those which lead to the formation of the alkyl halide. In the preparation of alkyl bromides and iodides by this method it is not necessary to use halides of phosphorus, which have been prepared previously. Red phosphorus is added to the alcohol, and bromine or iodine is then cautiously added. The phosphorus halide formed interacts with the alcohol. After standing for some time the mixture is distilled. Ethyl iodide is conveniently prepared in this way. 

Alcohols can be converted into other kinds of compounds having the same carbon skeleton. Alkyl halides are prepared from alcohols by use of hydrogen halides or phosphorus halides. Phosphorus halides are often preferred because they tend less to bring about rearrangement. The general equation for this reaction is as follows ... 

Reaction of an alcohol with the halogen acid (e.g. from NaBr + H2SO4) or with phosphorus halides (red phosphorus and iodine can be used) ... 

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