Thionyl. chloride

Thionyl chloride (SOCl2) is the most versatile of all sulfur transfer reagents in heterocyclic synthesis. The sulfur-oxygen bond renders the sulfur atom more electrophilic the possibility of ready removal by elimination of the oxygen atom allows easy aromatization of many of the initially formed sulfur heterocycles. Two general reviews of the chemistry of thionyl chloride are available.53 Both cover the literature up to about 1970. 

Manufacture Thionyl chloride is manufactured by reacting sulfur dioxide or sulfur trioxide with sulfur dichloride and chlorine or with disulfur dichloride and chlorine  

Sulfur dichloride has to be used as a reaction partner for sulfur oxides in all cases. 

Thiocarbonyl Transfer. While virtually all uses of TCDI involve a thiocarbonyl transfer reaction, this section covers those uses of the thiocarbonyl transfer that do not lead to radical chemistry or alkene syntheses. TCDI has been used for the simple placement of a thiocarbonyl group between two nucleophilic atoms of one or two molecules. An alcohol which has been converted to an imidazolide is a reactive functionality for coupling reactions, for sigmatropic rearrangements, and for elimination (eq 8). The TCDI alternative l,r-thiocarbonyl-2,2 -pyridone seems to be an excellent thiocarbonyl transfer agent. 

Adrian L. Schwan University of Guelph, Ontario, Canada 

Purification impurities cause formation of yellow or red colors. Iron contamination can cause a black color. Fractional distillation, either directly or from triphenyl phosphite or quinoline and linseed oil, has been recommended. 

Chlorides from Alcohols. Thionyl chloride reacts with primary, secondary, and tertiary alcohols to form chlorosulfite esters (eq 1) which can be isolated. The fate of these esters depends on the reaction conditions, especially the stoichiometry, solvent, and base. If 2 equiv of alcohol and pyridine are used relative to thionyl chloride, dialkyl sulfites may be isolated (eq Z).  

When thionyl chloride is in excess, or when alkyl chlorosulfites are treated with thionyl chloride, alkyl chlorides are produced and the byproducts are HCl and SOi- The mechanism of this reaction may be Sn 1, Sn2, SNi, or Sn2 (with allylic or propargylic alcohols). In the absence of base the SnI mechanism operates retention of configuration is observed in the alkyl chloride (eq 3). Considerable ionic character may be involved in this process and small amounts of elimination or rearrangement are common as side reactions.  

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A -dialkylchloroalkylamines, R2N(CH2)nCI. Formed by treating the alkanolamine with thionyl chloride. Of importance in the synthesis of pharmaceuticals, particularly tranquillizers, e.g. amidons. 

Sulphur tetrachloride, SCI4, m.p. 30 C. Stable only in the solid. The oxide chloride of sulphur(lV) is SOCI2, thionyl chloride. ... 

SULPHUR DICHLORIDE OXIDE, THIONYL CHLORIDE, SOClj... 

Sulphur dichloride oxide (thionyl chloride) on the hydrated chloride can also be used to produce the anhydrous chloride in certain cases, for example copper(II) chloride and chromium(III) chloride ... 

One disadvantage of this method is that it is sometimes difficult to separate the acid chloride sharply from the phosphorus oxychloride by fractional dis tillation, and unless the boiling oints of these two substances are fairly wide apart, traces of the oxychloride will occasionally pass over in the vapour of the acid chloride. If, however, thionyl chloride is used instead of phosphorus... 

Place 20 g. of dry powdered benzoic acid in C, add 15 ml. (25 g., i.e., a 30% excess) of thionyl chloride and some fragments of porcelain, and then clamp the apparatus on a boiling water-bath as shown so that no liquid can collect in the side-arm of C. Heat for one hour (with occasional gentle shaking), by which time the evolution of gas will be complete. Cool the flask C, detach the condenser and fit it to the side-arm for distillation, using a 360° thermometer for the neck of C. To the lower end of the condenser fit a small conical flask G (Fig. 67(B)) by a cork carrying also a calcium chloride tube. 

Now distil the contents of C by heating carefully over a gauze. A small initial fraction of unchanged thionyl chloride boiling at 78-80° comes over, and the temperature then rises rapidly to 194°. Directly this happens, stop the distillation, allow the condenser to drain thoroughly, and then replace G by the duplicate receiver. Run the water out of the condenser so that it acts as an air-condenser, and then continue the distillation. Collect the benzoyl chloride as the fraction boiling at 194-198°. Yield, 19 g. 

In the distilling-flask remains a very small high-boiling fraction of benzoic anhydride (b.p. 366 ), formed by the dehydrating action of the thionyl chloride on the benzoic acid ... 

Method 1. Mix 1 0 g. of 3 5-dinitrobenzoic acid (Section IV,168) with 4 ml. of thionyl chloride in a dry 50 ml. conical flask fit a reflux condenser, carrying a plug of cotton wool at the upper end, into the flask and heat on a water bath for 15-30 minutes. Remove the condenser and heat the flask in a boiling water bath FUME CUPBOARD 1) until the excess of thionyl chloride has evaporated. Use the resulting 3 5-dinitrobenzoyl chloride (about 10 g.) immediately. 

The melting points of these esters are usually much lower than those of the corresponding 3 5 dinitrobenzoates their preparation, therefore, offers no advantages over the latter except for alcohols of high molecular weight and for polyhydroxy compounds. The reagent is, however, cheaper than 3 5 dinitrobenzoyl chloride it hydrolyses in the air so that it should either be stored under light petroleum or be prepared from the acid, when required, by the thionyl chloride or phosphorus pentachloride method. 

By the action of thionyl chloride upon the alcohol alone or mixed with pyridine (to absorb the hydrogen chloride formed in the reaction), for example ... 

The dichlorides of aliphatic glycols are obtained by reaction with thionyl chloride in the presence of a small quantity of pyridine, for example ... 

Fit a 500 ml. round-bottomed flask with a dropping funnel and a double surface condenser alternatively, the flask may be provided with a two-way addition tube (Fig. II, 13, 9) and the dropping funnel and condenser inserted into the latter. Place 37 g. (46 ml.) of iso-butyl alcohol (b.p. 106-108°) and 40 g. (41 ml.) of pure pyridine in the flask and 119 g. (73 ml.) of redistilled thionyl chloride in the dropping funnel. Insert a cotton wool or calcium chloride guard tube into the mouth of the funnel. Introduce the thionyl chloride during 3-4 hours a white solid... 

The lower pyridine layer contains most of the excess of thionyl chloride it may be recovered by distillation through an efficient fractionating column. 

Place 179 g. (109-5 ml.) of redistilled thionyl chloride in the 250 ml. Claisen flask and 51 g. (62-6 ml.) of n-hcxyl alcohol, b.p. 156-158°, in the separatory funnel. Add the nr-hexyl alcohol during 2 hours there is a slight evolution of heat, sulphur dioxide is evolved (hence carry out the... 

Dichlorobutane. Place 22-5g. of redistilled 1 4-butanediol and 3 ml. of dry pyridine in a 500 ml. three necked flask fitted with a reflux condenser, mechanical stirrer and thermometer. Immerse the flask in an ice bath. Add 116 g. (71 ml.) of redistilled thionyl chloride dropwise fix>m a dropping funnel (inserted into the top of the condenser) to the vigorously stirred mixture at such a rate that the temperature remains at 5-10°. When the addition is complete, remove the ice bath, keep the mixture overnight, and then reflux for 3 hours. Cool, add ice water cautiously and extract with ether. Wash the ethereal extract successively with 10 per cent sodium bicarbonate solution and water, dry with anhydrous magnesium sulphate and distil. Collect the 1 4-dichloro-butane at 55-5-56-5°/14 mm. the yield is 35 g. The b.p. under atmospheric pressure is 154 155°. 

Alkyl sulphites. From the alcohol and thionyl chloride, for example 2C,H, OH + SOClj —> (C,H, )jS03 + 2HC1... 

Fit up the apparatus shown in Fig. Ill, 31, 1 the capacity of the Claisen flask should be 100 ml. Place 40 g. (24-6 ml.) of redistilled thionyl chloride in the flask and 60 g. (62 ml.) of dry n-butyl alcohol (b.p. 116-117°) in the dropping funnel. Cool the flask in ice and add the n-butyl alcohol, with frequent shaking, over 1 hour (1). Reflux the mixture gently for 1 hour to complete the reaction and to remove the residual hydrogen chloride. Arrange the apparatus for distillation, and distil under normal pressure until the temperature rises to 120° then distil under diminished pressure (Fig. 11, 20, 1) and collect the di-n-butyl sulphite at 116-118°/20 mm. The yield is 66 g. 

Amides, anilides and p toluidides. The dry acid is first converted by excess of thionyl chloride into the acid chloride ... 

Stopper the side arm of a 25 or 50 ml. distilling flask and fit a vertical water condenser into the neck. Place 0-5-1 -0 g. of the dry acid (finely powdered if it is a solid) into the flask, add 2-5-5 0 ml. of redistilled thionyl chloride and reflux gently for 30 minutes it is advisable to place a plug of cotton wool in the top of the condenser to exclude moisture. Rearrange the condenser and distil off the excess of thionyl chloride t (b.p. 78°). The residue in the flask consists of the acid chloride and can be converted into any of the derivatives given below. 

Place 1 0 g. of the monobasic acid and 2 g. of aniline or p-toluidine in a dry test-tube, attach a short air condenser and heat the mixture in an oil bath at 140-160° for 2 hours do not reflux too vigorously an acid that boils below this temperature range and only allow steam to escape from the top of the condenser. For a sodium salt, use the proportions of 1 g. of salt to 1 5 g. of the base. If the acid is dibasic, employ double the quantity of amine and a reaction temperature of 180-200° incidentally, the procedure is recommended for dibasic acids since the latter frequently give anhydrides with thionyl chloride. Powder the cold reaction mixture, triturate it with 20-30 ml. of 10 per cent, hydrochloric acid, and recrystallise from dilute alcohol. 

Thionyl chloride. This reagent (b.p. 76°) is generally used in excess of the theoretical quantity it cannot be employed for acetyd chloride (b.p. 52°) because of the difficulty of separation by fractional distillation. Excellent results are obtained, however, with butyrric acid and acids of higher molecular weight, for example ... 

The reason for using an excess of,sny, 1 mol of thionyl chloride is to avoid anhydride formation ... 

The excess of thionyl chloride displaces the equilibrium to the left not only by removing the carboxylic acid (RCOOH + SOClj->RCOCl + SOj + HCl) but also by... 

Prepare n-heptoyl chloride from the acid by treatment with thionyl chloride as detailed for n-butyryl chloride (Section 111,87) b.p. 173-175°. 

From the acid chloride. By the interaction of the acid chloride (prepared from the acid and thionyl chloride) and the calculated quantity of the alcohol at 0°, for example ... 

Ethyl cyctopropane-carboxylate. Use 22 g. of cyciopropane-carb-oxyhc acid (Section V,33) and 40 g. (24-5 ml.) of redistiUed thionyl chloride to prepare the acid chloride, b.p. 118-119° (22 g.). Treat the latter with 10-1 g. of absolute ethyl alcohol. The yield of ethyl cyclo-propane-carboxylate, b.p. 132-133°, is 13 g. 

Fit a reflux condenser into the short neck of a 125 ml. Claisen flask, a separatory funnel into the long neck, and plug the side arm with a small cork (compare Fig. Ill, 31, 1). Place 58 g. (62 ml.) of commercial n-caproic acid (1) in the flask and heat on a water hath. Add 75 g. (46 ml.) of redistilled thionyl chloride through the separatory funnel during 45 minutes shake the flask from time to time to ensure thorough mixing. Reflux the mixture for 30 minutes. Arrange the apparatus for distillation from an air bath (Fig. II, 5, 3) the excess of thionyl chloride passes over flrst, followed by n-caproyl chloride at 145-155° (mainly at 150-155°). The yield of acid chloride is 56 g. 

Place 29 g. of n-caproamide (Section 111,109) into a 200 ml. distilling flask, and assemble the apparatus shown in Fig. Ill, 28, 1. Remove the trap momentarily and introduce 45 g. (27-5 ml.) of redistilled thionyl chloride no apparent reaction takes place in the cold. Warm the mixture on a water bath or by means of a small flame for 1 hour. Arrange the apparatus for distillation and distil oflF the excess of thionyl chloride (t.c., until the temperature reaches about 90°) and allow to cool. When cold, transfer the residue to a 100 ml. distilling flask (1). Distil from an air bath (Fig. II, 5, 3) the n-capronitrile passes over at 161-163° (2). The yield is 21 g. 

Commercial 2 4-dichlorophenoxyacetic acid may be recrystallised from benzene m.p. 139-140°. Reflux 10 g. of the acid with 15 ml. of thionyl chloride on a steam bath for 1 hour, distil off the excess of thionyl chloride at atmospheric pressure and the residue under reduced pressure 2 4-dichlorophenoxyacetyl chloride (8 g.) passes over at 155-157°/22-23 mm. It occasionally crystallises (m.p. 44-5-45-5°), but usually tends to remain as a supercooled liquid. 

The phenyl propionate may be prepared by slowly adding 196 g. (120 ml.) of redistilled thionyl chloride to a mixture of I50g. of pure phenol and 132 g. (133 ml.) of propionic acid (compare Fig. 111,31, 1), warming to drive all the sulphur dioxide and hydrogen chloride, and distilling 190 g. of phenyl propionate, b.p. 202-212° (the pure substance boils at 211°) are obtained. 

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