Thionyl chloride with alcohols

Reaction of alcohols with thionyl chloride (Section... 

Reaction of alcohols with thionyl chloride (Section 4.13) Thionyl chloride is a synthetic reagent used to convert alcohols to alkyl chlorides. 

The example shown is the most important case of this mechanism yet discovered, since the reaction of alcohols with thionyl chloride to give alkyl halides usually proceeds in this way, with the first step in this case being ROH -I- SOCI2 ROSOCl (these alkyl chlorosulfites can be isolated). 

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... 

A careful investigation of the extent of isomeric products formed by reaction of several alcohols with thionyl chloride has been reported. The product compositions for several of the alcohols are given below. Identify the structural features that promote isomerization and show how each of the rearranged products is formed. 

Treatment of bipyridine-dicarboxylic acid 191 in alcohols with thionyl chloride and gaseous chlorine furnished the corresponding trichloroindolizines 193 through the intermediary of diesters 192 (Scheme 6) <2002J(P 1) 1688, 2002MI1, 2002MOL628>. 

In 1963, an asymmetric synthesis of chloroallenes was reported by the SNi reaction of propargyl alcohols with thionyl chloride [34]. Since then, rearrangement of pro-pargylic precursors has been one of the most useful methodologies for the synthesis of allenes [35]. Treatment of 84, obtained by asymmetric reduction with LiAlH4-Dar-von alcohol complex, with thionyl bromide gave 86 as the major product via 85 (Scheme 4.21) [36],... 

The reaction of primary or secondary alcohols with thionyl chloride is a general method far preparing the corresponding chlaro compounds. In the first step a chlorosulfue ROSOG is formed from which S02 is eliminated in a relatively slow step. This decomposition is... 

The topical antifungal bifonazole (60-2) dispenses with virtually all but the imidazole ring the intermediate (60-1) is obtained by sequential reduction of 4-phenyl-benzophenone and then reaction of the alcohol with thionyl chloride. Displacement of chlorine by imidazole gives (60-2) [65]. 

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). 

Halogenoalkylquinuclidines were prepared by the reaction of the corresponding alcohols with thionyl chloride or halogen acids.24,49,121>... 

Rearrangement may be largely (but not entirely) suppressed by preparing the alkyl chloride from a reaction of the alcohol with thionyl chloride, either (i) alone, or (ii) in the presence of catalytic or equimolar proportions of pyridine, or (iii) in the presence of dimethylformamide.85 In (i) a chlorosulphite is first formed which decomposes via two sequentially formed ion-pair species the second ion pair collapses to yield the alkyl chloride. 

The reaction of primary or secondary alcohols with thionyl chloride is a general method for preparing the corresponding chloro compounds. In the first step a chlorosulfne ROSOC) is formed from which S02 is eliminated in a relatively slow step. This decomposition is facilitated by a tertiary amine, e.g. pyridine. The ammonium salt RO-SON+.Cl— formed from the chlorosulftte is subsequently attacked on carbon (in R) by CF. Since nucleophilic substitutions on propargylic carbon proceed more easily than on carbon in saturated compounds, it may be expected that the conversion of propargylic chlorosulfites into the chlorides will take place under relatively mild conditions. 

Mechanism of the reaction of an alcohol with thionyl chloride to produce an alkyl chloride. 

Reaction of an Alcohol with Thionyl Chloride Section 10.5 Figure 10.3... 

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... 

The mechanisms of these reactions begin like the reaction of an alcohol with thionyl chloride. Either oxygen atom of the acid can attack sulfur, replacing chloride by a mechanism that looks like sulfur s version of nucleophilic acyl substitution. The product is an interesting, reactive chlorosulfite anhydride. 

The direct dehydration of aliphatic y3-nitro alcohols to nitro olefins is usually unsatisfactory. The latter compounds are obtained by method 24 or by treating the nitro alcohols with thionyl chloride and pyridine, ... 

The treatment of a 1° or 2° alcohol with thionyl chloride, SOCI2, and pyridine forms an alkyl chloride, with SO2 and HCI as by-products. 

An exception to these general principles which has been reported is the reaction of a- or 7-ethylallyl alcohol with thionyl chloride. The primary isomer gives principally the secondary chloride, and from the secondary isomer the primary chloride predominates.4 It has been pointed out, however,5 that these results may be explained by an Sni type reaction of the intermediate chlorosulfinic ester in which a six-membered ring is involved. Thus for the transformation of a-ethylallyl alcohol (VIII) to 7-ethallyl chloride (IX), we have ... 

Alkyl chlorides can be prepared by the reaction of alcohols with thionyl chloride (SOCl2) in the presence of a nitrogen base (e.g. triethylamine or pyridine). An intermediate alkyl chlorosulfite (ROSOC1) is formed by nucleophilic attack of ROH on the sulfur atom of thionyl chloride. The OH group is converted to an OSOCl-leaving group, which is displaced on reaction with the chloride anion (e.g. in an SN2 mechanism when R is a primary alkyl group). 

ROH —> RCl. In some instances zinc chloride has been found to be more effective than pyridine, the usual catalyst (1, 1160-1161), in the reaction of alcohols with thionyl chloride. The reaction proceeds mainly with inversion of configuration. ... 

The mechanism for the reaction of phosphorus tribromide with alcohols is similar to that for the reaction of alcohols with thionyl chloride. The alcohol reacts with PBr3 giving an intermediate of the type ROPBr2 which reacts with the nucleophilic bromide ion. 

Early examples of the substitution of a-hydroxysilanes with chloride employ thionyl chloride as the reagent. The transformation is achieved simply by mixing the alcohol with thionyl chloride in diethyl ether (19 —> 20, Scheme 5). A benzylsilyl group is not cleaved by the hydrochloric add produced under these conditions. The reaction has not seen many applications, probably because the yields are not generally high. This has prompted the development of other methods (Sections 4.4.27.2.2 and 4.4.27.2.3). 

The Sni mechanism (substitution-nucleophilic-internal), as originally proposed, postulated a front-side displacement occurring via a four-center transition state. It is now clearly established that such a process has never been observed, and that all the reactions proposed to proceed by SnI mechanisms involve ion pairs. The Sni mechanism was initially suggested to explain the observed stereochemistry of chlorosulfite decomposition. Chlorosulfite esters are formed by reaction of alcohols with thionyl chloride, and are the key reactive intermediates in the conversion of alcohols to chlorides with thionyl chloride. Nucleophilic attack by the chloride of the chlorosulfite ester was considered to be concerted with cleavage of the C-O bond ... 

Reaction of an alcohol with thionyl chloride in the presence of a tertiary amine (e.g., pyridine) aflFords replacement of the OH group by Cl with inversion of configuration (Section 11.9). However, if the amine is omitted, the result is usually replacement with retention of configuration. The same chlorosulfite intermediate is involved in both cases. Suggest a mechanism by which this intermediate can give the chlorinated product without inversion. 

A few nucleophilic substitution reactions have been observed to proceed with a high degree of retention of configuration. One example is reaction of alcohols with thionyl chloride, which under some conditions gives predominantly product of retained configuration. This reaction is believed to involve formation of a chlorosulfite ester. This can then react with chloride to give inverted product. 

---