Sulfonyl chloride formation, chlorination

Sulfonyl chloride formation, chlorination of S-alkylisothiuronium salts, 141 sodium sulfonate and PCls, 208... 

The addition sequence may determine the primary reaction course or influence impurity formation. For example, condensation of diethyl 3-oxoglutarate 33 with chloroacetone and methylamine is expected to give the 5-methylpyrrole 34, the Hantzch pyrrole product (Figure 5.14). The isomeric 4-methylpyrrole 35 (a precursor to zomepirac sodium) was prepared in good yield by first treating 33 with methylamine, then adding chloroacetone [22]. The addition sequence was also important for the chlorination of the sulfinate anion 36 The dimer 37 was produced when N-chlorosuccinimide was added to the reaction, but when 36 was added slowly to excess Cl2, the desired sulfonyl chloride 38 was produced (Figure 5.14) [23], The course of these reactions may be predicted if one takes a mental snapshot of them. 

Treatment of benzothiazole with an excess of chlorosulfonic acid and then thionyl chloride affords a 4 1 mixture of the 4- and 7-sulfonyl chlorides, respectively. Chlorosulfonic acid alone fails to react with benzothiazole. This is probably due to the formation of the 4-sulfonic acid where an intramolecular hydrogen bond inhibits the formation of the chlorinated derivative <92PS(73)107>. Interestingly, when the same reaction is carried out with 2-methylbenzothiazole the major product is the 6-sulfonyl chloride. 

The present study reflects the re-design of a manufacturing process for the production of a copper phthalocyanine dye intermediate through a three step process involving synthesis, precipitation, and filtration. Figure 1 shows the reaction scheme for the original process. The sulfonation of copper phthalocyanine with chlorosulfonic acid is followed by a chlorination step with thionyl chloride that leads to the formation of the tetra-sulfonyl chloride dye intermediate. The product is isolated via a water precipitation (quenching) from the acidic solution followed by a filtration operation. 

A standard condition has been optimized for this reaction, in which the aryl amine is diazotized in 10 times its amount of acetic acid, followed by the addition of one equivalent of cuprous halide in hydrohalic acid. Under these conditions, the acetate salt of aryl amine is relatively soluble, and less froth and tarry material are formed during diazo transformation. In addition, chlorination, bromination, and iodonation of p-haloaniline to dihalobenzenes under such standard conditions give almost comparable average yields. Other modifications of this reaction include the formation of phenyl selenocyanate by the reaction with potassium selenocyanate, and aryl nitrile by the reaction with nickel cyanide. Moreover, this reaction has been extended to the preparation of phenyl thiocyanate, phenyl isothiocyanate and aromatic sulfonyl chloride. ... 

A mechanism was proposed" for the conversion of 59—>60 involving initial formation of the sulfonyl chloride 61 which subsequently suffered thermal decomposition with loss of sulfur dioxide and formation of pentachlorobenzene 62. Finally repetition of these steps gave hexachlorobenzene 60, as indicated in Equation 17. The mechanism is in agreement with the observation that several arylsulfonyl chlorides undergo thermal decomposition with concomitant chlorination." ... 

The chloride of triflic acid (trifluoromethanesulfonyl chloride) is an effective sulfonylating agent Like triflic anhydride, it usually reacts with alcohols and other nucleophiles with the formation of the corresponding derivatives of tnflic acid [69] However, in some reactions, it acts as a chlorinating reagent [98] The reactions of tnfluoromethanesulfonyl chloride with 1,3-dicarbonyl compounds or some carboxylic esters in the presence of a base result m the formation of chlonnated products in high yields (equation 49)... 

Perfluorophenylsulfonyl chloride and its 4-substituted derivatives 5 are prepared from reaction of the thiols 4 with chlorine in acetic containing the amount of water calculated for formation of the sulfonyl group.287 The initially formed precipitate of disulfide is slowly dissolved, Surprisingly, in the case of the 4-acetamido derivative, the oxidation is accompanied with desulfuration. The use of hydrogen peroxide does not have a substantial influence on the desulfuration process.287... 

Again, Hess and Ljubitsch106 remarked that a combination of the phenomena of sulfonylation, chlorination, and quaternization failed to provide a coherent explanation for their observations on the prolonged treatment of cellulose with tosyl chloride in pyridine. Re-examination thereof, with special attention to the possible formation of anhydro rings (and, perhaps, of double bonds), is indicated. 

Even with TPS, a small amount of sulfonation is observed. Further, release of hydrogen chloride, even though scavenged by the pyridine solvent, can cause unwanted side reactions, especially if acid sensitive functions are present. Both problems have been solved by replacing the chlorine with imidazole, triazole and tetrazole leaving groups. Thus, the sulfonyl agents available for phosphodiester formation are as follows ... 

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