Thionyl chloride formation

Diphenyl-3-nitro-2-pyrazinone (85) undergoes displacement of the nitro group (cf. Section II,D,2,c) by halide ion in aqueous acid (protonation of the 0x0 oxygen atom), with thionyl chloride (formation of —0—SO—Cl which in this case does not go to chloro), and with phosphorus oxychloride [formation of —0— POCl2 (86) which goes to chloro, but more slowly than nitro displacement occurs]. 

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

A large excess of thionyl chloride is recommended in order to avoid the format tion of p-nitrobenzoic anhydride (see Note 1 to Section IV,185). 

Formation of the acid chloride, e.g., with thionyl chloride or with phosphorus pentachloridc ... 

A simpler nonphosgene process for the manufacture of isocyanates consists of the reaction of amines with carbon dioxide in the presence of an aprotic organic solvent and a nitrogeneous base. The corresponding ammonium carbamate is treated with a dehydrating agent. This concept has been apphed to the synthesis of aromatic and aUphatic isocyanates. The process rehes on the facile formation of amine—carbon dioxide salts using acid haUdes such as phosphoryl chloride [10025-87-3] and thionyl chloride [7719-09-7] (30). 

Monsanto has disclosed the use of carbon dioxide—amine complexes which are dehydrated, at low temperatures, with phosphoryl chloride [10025-87-3] or thionyl chloride [7719-09-7] as a viable route to a variety of aUphatic isocyanates. The process rehes on the facile formation of the intermediate salt (30).REPLACEVariations of this process, in which phosgene is used as a dehydrating agent, have been reported earlier (84). Table 2 Hsts commercially available aUphatic isocyanates. 

Acid Chloride Formation. Monoacid chlorides of maleic and fumaric acid are not known. Treatment of maleic anhydride or maleic acid with various reagents such as phosgene [75-44-5] (qv), phthaloyl chloride [88-95-9] phosphoms pentachloride [10026-13-8] or thionyl chloride [7719-09-7] gives 5,5-dichloro-2(5JT)furanone [133565-92-1] (4) (26). Similar conditions convert fumaric acid to fumaryl chloride [627-63-4] (5) (26,27). NoncycHc maleyl chloride [22542-53-6] (6) forms in 11% yield at 220°C in the reaction of one mole of maleic anhydride with six moles of carbon tetrachloride [56-23-5] over an activated carbon [7440-44-4] catalyst (28). 

Sahcyhc acid can be converted to sahcyloyl chloride [1441 -87-8] hy reaction with thionyl chloride in boiling ben2ene. The formation of acyl haUde may also extend to reaction with the phenoHc hydroxyl. The reaction with phosphoms tri- and pentachlorides is not restricted to the formation of the acid chloride. Further interaction of the phosphoms haUde and the phenoHc hydroxyl results in the formation of the phosphoric or phosphorous esters. 

Acid Chloride Formation. Neopentanoic acid can be converted to neopentanoyl chloride [3282-30-2] by reaction with thionyl chloride (2), phosgene (3), phosphoms pentachloride, phosphoms trichloride, or by the reaction with henzotrichloride ia the presence of Eriedel-Crafts catalysts (4). A laboratory procedure usiag tetramethyl-a-halogenoenamines at room temperature has also been reported (5). 

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

Treatment of valeroidine hydrobromide with thionyl chloride in an attempt to replaee the hydroxyl group by chlorine resulted in demethylation with the formation of norvaleroidine, a syrup yielding a crystalline hydrobromide, C12H21O3N. HBr, m.p. 270°, -)- 1° (c = 20 ... 

One of the most widely used systems for dehydration is the combination of phosphorous oxychloride and pyridine. This reagent is apparently incompatible with the A" -3-keto system/ probably due to formation of a phosphorylated enol. It is, however, more selective than thionyl chloride-pyridine since 17a-alcohols are not dehydrated ... 

A -01efin formation can be avoided with thionyl chloride-pyridine by keeping the exposure brief and operating at low temperature in addition, the reagent may be used in the presence of a A" -3-ketone ... 

Potassium nitrite by-product can react with nitroaromatic substrate to suppress yields of aryl fluorides Modest yields (40-60%) of fluorophthafic anhydride are obtained from 3- or 4-nitiophthalic anhydride and potassium fluonde due to formation of by-product dipotassium salt of 3- or 4-nitrophtlialic acid [1/3,114, 115] (equation 33) Higher yields (93%) of 3-fluorophfhalic anhydride can be realized by regenera tion of 3-nitrophthalic anhydride from the dipotassium salt with thionyl chloride, followed by addition of fresh potassium fluoride [7/5] (equation 33)... 

N,N - Bis(trimethylsilyl)sulfur(rV) diimide Me3SiN=S=NSiMc3 is an especially versatile source of the N=S=N functionality in the formation of both acyclic and cyclic S-N compounds. It is conveniently prepared by the reaction of NaN(SiMc3)2 and thionyl chloride (Eq. 2.5). 

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... 

Treatment of pyridyl carbinol 51 with thionyl chloride leads to the corresponding chloride (52), Treatment of that intermediate with 5-methoxy-2-mercaptobenzimidazole (53), obtained from reaction of 4-methoxy-q-phenylenediamine with potassium ethylxanthate leads to displacement of halogen and formation of the sulfide (54). Finally, oxidation with 3-chloroperbenzoic acid produces the sulfoxide omeprazole (55) fl7]. 

A solution of 54.1 grams of 1-formyl-4-(3 -chloropropyl)-piperazine, [prepared by formylat-ing 1-(3 -hydroxypropyl)-piperazine by refluxing in an excess of methyl formate, purifying the 1-formyl-4-(3 -hydroxypropyl)-piperazine by vacuum distillation, reacting this compound with an excess of thionyl chloride at reflux and isolating the desired 1-formyl-4-(3 -chloropropyl)-piperazine by neutralization with sodium carbonate solution followed by distillation] in 200 ml of toluene is added. The reflux period Is continued for 4 hours. 

Benzothiepins synthesized by a double Knoevenagel condensation (see Section 2.1.1.2.) contain free carboxylic acid groups if the reaction product is isolated under acidic conditions. Rcesterification can be performed by two methods via formation of the acid chloride and subsequent alcoholysis, or by reaction with diazomethane, e.g. the conversion of 3-benzo-thiepin-2,4-diearboxylic acid (5, R = C02H) with thionyl chloride and methanol gives the dimethyl ester 5 (R = C02Me) in 47% yield, while the diazomethane pathway provides 60% of the dimethyl ester.65 Use of excess diazomethane leads to cycloadducts (see Section 2.2.4.). 

Satisfactory sebacoyl chloride can be purchased from the Eastman Kodak Co., Rochester, New York. The submitters prepared it as follows. A mixture of 150 g. (0.74 mole) of sebacic acid and 150 ml. of thionyl chloride is heated in a water bath at 60°. The acid gradually goes into solution with evolution of sulfur dioxide and hydrogen chloride. When gas evolution ceases, the mixture is distilled as rapidly as possible under reduced pressure. The yield of sebacoyl chloride, b.p. 171-175°/15 mm., is about 140 g. (79%). Caution1 Toward the end of the distillation, spontaneous decomposition of the residue with formation of a voluminous black foam frequently occurs. 

Thionyl chloride is another activating agent employed for reactions between aromatic carboxylic acids and phenols in pyridine solution. The mechanism suggested does not involve the formation of an acid chloride but assumes the existence of an intermediary mixed sulfinic anhydride which undergoes reaction with phenolic endgroups (Scheme 2.32).311... 

Many procedures for the formation of carboxylic acid amides are known in the literature. The most widely practiced method employs carboxylic acid chlorides as the electrophiles which react with the amine in the presence of an acid scavenger. Despite its wide scope, this protocol suffers from several drawbacks. Most notable are the limited stability of many acid chlorides and the need for hazardous reagents for their preparation (thionyl chloride, oxalyl chloride, phosgene etc.) which release corrosive and volatile by-products. Moreover, almost any other functional group in either reaction partner needs to be protected to ensure chemoselective amide formation.2 The procedure outlined above presents a convenient and catalytic alternative to this standard protocol. 

Evidence for this mechanism is as follows The addition of pyridine to the mixture of alcohol and thionyl chloride results in the formation of alkyl halide with inverted configuration. Inversion results because the pyridine reacts with ROSOCl to give ROSONC5H5 before anything further can take place. The Cl freed in this process now attacks from the rear. The reaction between alcohols and thionyl chloride is second order, which is predicted by this mechanism, but the decomposition by simple heating of ROSOCl is first order. ... 

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 traditional method for transforming carboxylic acids into reactive acylating agents capable of converting alcohols to esters or amines to amides is by formation of the acyl chloride. Molecules devoid of acid-sensitive functional groups can be converted to acyl chlorides with thionyl chloride or phosphorus pentachloride. When milder conditions are necessary, the reaction of the acid or its sodium salt with oxalyl chloride provides the acyl chloride. When a salt is used, the reaction solution remains essentially neutral. 

Reacts with vapors of sodium with luminescence at about 260°C. Reacts explosively with thionyl chloride or potassium reacts violently with hexafluoro isopropylidene, amino lithium, ammonia, and strong acids reacts with tert-butyl azidoformate to form explosive carbide reacts with 24-hexadiyn-l, 6-diol to form 2, 4-hexadiyn-l, 6-bischloro-formate, a shock-sensitive compound reacts with isopropyl alcohol to form isopropyl chloroformate and hydrogen chloride thermal decomposition may occur in the presents of iron salts and result in explosion. 

There are also some rare domino sequences where two anionic and two radical reactions are combined (Scheme 2.152) [347]. According to a report of the Wang group, thionyl chloride is able to promote a succession of reactions by an initial formation of a chlorosulfite 2-673 of the tertiary alcohol 2-672, followed by an SN-type reaction to produce the chloroallene 2-674. A Schmittel cyclization reaction [348] then generates... 

Another example has been provided by Ito et al., who described the use of methanofullerene derivatives as powerful and stable precursors for glycofullerenes.217 Their study was based on the use of [60]fullerenoacetyl chloride (227), obtained from the ferf-butyl [60]fullerenoacetate derivative 226, which had been prepared in 56% yield by treatment of corresponding stabilized sulfonium ylides 225 with C6o-218 Subsequent transformation with p-TsOH in toluene gave [60]full-erenoacetic acid, which was directly converted into the corresponding acyl chloride 227 by using thionyl chloride. Standard ester formation with methyl 2,3,4-tetra-O-benzyI -/<-d-gl ucopyranoside (228) and 4-(dimethylamino)pyridine (DMAP) afforded the desired hybrid derivative 229 in 66% yield. 

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