Thionyl Chloride rearrangement reactions

Synthesis of the remaining half of the molecule starts with the formation of the monomethyl ether (9) from orcinol (8). The carbon atom that is to serve as the bridge is introduced as an aldehyde by formylation with zinc cyanide and hydrochloric acid (10). The phenol is then protected as the acetate. Successive oxidation and treatment with thionyl chloride affords the protected acid chloride (11). Acylation of the free phenol group in 7 by means of 11 affords the ester, 12. The ester is then rearranged by an ortho-Fries reaction (catalyzed by either titanium... 

Primary and secondary alcohols are best converted into alkyl halides by treatment with either thionyl chloride (SOCl2) or phosphorus tribromicle (PB ). These reactions, which normally take place readily under mild conditions, are less acidic and less likely to cause acid-catalyzed rearrangements than the HX method. 

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. 

The synthesis of the benzoimidazo[l,2- ][l,2,3]thiadiazole 61 can be explained using the same mechanistic model to that used for the Hurd-Mori reaction. The amino benzimidazole 58 when treated with thionyl chloride at reflux affords the benzoimidazo[l,2-r ][l,2,3]thiadiazole 61. If, however, the reactant 58 is treated with thionyl chloride at room temperature, the chloromethyl derivative 59 is formed. This derivative was then transformed into product 61 on reflux with thionyl chloride. The proposed mechanism for the formation of product 61 is for the initial formation of the sulfoxide 60, which then undergoes a Pummerer-like rearrangement, followed by loss of SO2 and HC1 to give the c-fused 1,2,3-thiadiazole 61 (Scheme 7) <2003TL6635>. 

The sulfide derivative of furocoumarin based natural products can be synthesized by treatment of a thiadiazole 107 with KO-f-Bu and an organohalide in an one-pot operation. This process presumably involves the generation of a phenolate 108 and is followed by an intramolecular proton shift and a rearrangement to give an alkynethiolate 109, which undergoes a sequence of intramolecular proton shift, cyclization and alkylation to lead to the furocoumarin product. The thiadiazole, in turn, can be prepared by reaction of the corresponding acetyl precursor with carbethoxyhydrazine, followed by treatment with thionyl chloride . 

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],... 

Treatment of the propargylic alcohol 144, readily prepared from condensation between benzophenone (143) and the lithium acetylide 101, with thionyl chloride promoted a sequence of reactions with an initial formation of the chlorosulfite 145 followed by an SNi reaction to produce in situ the chlorinated and the benzannulated enyne-allene 146 (Scheme 20.30) [62], A spontaneous Schmittel cyclization then generated the biradical 147, which in turn underwent a radical-radical coupling to form the formal [4+ 2]-cycloaddition product 148 and subsequently, after a prototropic rearrangement, 149. The chloride 149 is prone to hydrolysis to give the corresponding 11 H-bcnzo h fluoren-ll-ol 150 in 85% overall yield from 144. Several other llff-benzo[fc]fluoren-ll-ols were likewise synthesized from benzophenone derivatives. 

Chinese chemists have reported the synthesis of pentacyclo[4.3.0.0 , 0 ]nonane-2,4-bis(trinitroethyl ester) (88). This compound may find potential use as an energetic plastisizer in futuristic explosive and propellant formulations. The synthesis of (88) uses widely available hydroquinone (81) as a starting material. Thus, bromination of (81), followed by oxidation, Diels-Alder cycloaddition with cyclopentadiene, and photochemical [2 - - 2] cycloaddition, yields the dione (85) as a mixture of diastereoisomers, (85a) and (85b). Favorskii rearrangement of this mixture yields the dicarboxylic acid as a mixture of isomers, (86a) and (86b), which on further reaction with thionyl chloride, followed by treating the resulting acid chlorides with 2,2,2-trinitroethanol, gives the energetic plastisizer (88) as a mixture of isomers, (88a) and (88b). Improvements in the synthesis of nitroform, and hence 2,2,2-trinitroethanol, makes the future application of this product attractive. 

Beckmann rearrangement of ketoketoximes 288 (R,R = alkyl, aryl) with thionyl chloride unexpectedly afforded 2-aryl(or alkyl)amino-4,6-disubstituted pyrylium salts 289 (equation 124). This reaction is the first example of rearrangement/cyclization involving carbonylic oxygen as terminator. ... 

Several steroidal cyclobntanone oximes were nsed to investigate the rearrangement reaction. The oxime 338, treated with thionyl chloride in benzene solution at room temperature, gave the expected pyrrolidinone 339 in 71% isolated yield (equation 127). 

The isomeric tricyclo[3.3.2.0 ]decane hydrocarbon (396) has also recently yielded to synthesis Thus, reaction of 394a with either thionyl chloride or phosphorus pentachloride led to rearrangement and formation of chloride 395a. Alternatively,... 

An unusual rearrangement provides the key to the preparation of a highly substituted pyrrolidone, doxapram (26-7), that is used as a respiratory stimulant. The synthesis starts with the displacement of chlorine on pyrrolidine (26-1) by the carbanion from diphenylacetonitrile (26-2) to give (26-3) as the product. The quite hindered nitrile is then hydrolyzed to the corresponding carboxylic acid (26-4) by basic hydrolysis. The reaction of acid with thionyl chloride presumably proceeds initially to form the corresponding acid chloride. The close proximity of that group to basic... 

The equivalence of sulfur and oxygen in this ring system carries over to NSAIDs as well. Preparation of the sulfur analogue of isoxepac (6-4) starts with the alkylation of thiophenol (27-1) with benzyl chloride (26-1). Cyclization of the intermediate thioether (27-2) then affords the homothioxanthone (27-3). The carboxyl side chain is then extended by means of the Amdt-Eistert homologation reaction. The acid is thus hrst converted to its acid chloride by means of thionyl chloride. Reaction with excess diazomethane leads to the diazoketone (27-4). Treatment of that intermediate with silver benzoate and triethylamine leads the ketone to rearrange to an acetic acid. There is thus obtained tiopinac (27-5) [28]. 

The acylation of 1,4-benzodiazepine 4-oxides, e.g. (230), leads to a Polonovski-type rearrangement giving (231) and provides a useful way of functionalizing the 3-position. Treatment of (230) with p-toluenesulfonyl chloride gives the quinoxalone (233) via a Beckmann type of rearrangement (72JHC747, p. 755) and similar rearrangements have been observed in the reactions of 4-hydroxy derivatives with thionyl chloride or phosphorus oxychloride. 

Quinoxaline-2-carboxylic acid with thionyl chloride gives the acid chloride (79%), which undergoes the expected reactions.166 The gas-phase pyrolysis of quinoxaline-2,3-dicarboxylic anhydride (157) over a Nichrome coil gives o-phthalonitrile (158) (72%), probably via 2,3-quinoxalyne (159) which ring-cleaves, and the diisocyanide subsequently rearranges thermally to the dinitrile.167... 

VI, obtained from stereospecific reactions of the corresponding optically active alcohol (11) with thionyl chloride, phosphorus pentachloride, etc., was not racemized under any of the reaction conditions. Monitoring the carbonyl absorption frequencies in the IR during these decarbonylations showed that the transformations II — III — IV took place during the conversion of V to racemic VI. Thus rearrangement or decomposition or both could be responsible for the racemization. 

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. 

Reaction in the absence of catalyst. Assemble in a fume cupboard a 500-ml three-necked flask equipped with a sealed stirrer unit, a double surface reflux condenser and a separatory funnel fit the condenser and the funnel with calcium chloride guard-tubes. Place 179 g (109.5 ml, 1.5 mol) of redistilled thionyl chloride in the flask and 51 g (62.5 ml, 0.5 mol) of hexan-l-ol, b.p. 156-158 °C, in the separatory funnel. Add the alcohol with stirring during 2 hours there is a slight evolution of heat, sulphur dioxide is evolved and the liquid darkens considerably. When all the alcohol has been added, reflux the mixture for 2 hours. Rearrange the apparatus for distillation, and distil slowly the excess of thionyl chloride passes over below 80 °C, followed by a small fraction up to 120 °C and finally the crude 1-chlorohexane at 132— 134 °C. Wash the last-named successively with water, 10 per cent sodium carbonate solution, and twice with water. Dry with anhydrous calcium chloride and distil through a short fractionating column. Pure 1-chlorohexane passes over at 133-134 °C. The yield is 36 g (60%). 

Af-Phenylhydroxylamine may be converted into an Af-benzoyl derivative by treating it in aqueous solution with benzoyl chloride while simultaneously removing, with sodium hydrogen carbonate, the liberated hydrogen chloride.32 On reaction with thionyl chloride this benzoyl derivative is converted into o-chlorobenzanilide (Expt 6.61) by way of an intermediate chlorosulphite ester, which then undergoes a specific ortho rearrangement.25... 

---