Thiophene-2-sulfonyl chloride

Thiophene-2-sulfonic acid, 5-acetamido-synthesis, 4, 932 Thiophene-3-sulfonic acid synthesis, 4, 932 Thiophene-2-sulfonyl chloride, synthesis, 4, 932... 

Thiophene-2-sulfonyl chloride, 4-nitro-synthesis, 4, 923 Thiophene-3-sulfonyl chloride synthesis, 4, 932 Thiophenetetracarboxylic acids esters... 

Thiophene is very easily sulfonated 95% H2SO4 at 30-40 °C converts it to the 2-sulfonic acid in a few minutes. Thiophene-2-sulfonyl chloride can be easily prepared by the action of chlorosulfonic acid on thiophene. Mono- and di-sulfonic acids of thiophene have been prepared by sulfonating thiophene with S03 or pyridine-sulfur trioxide (63AHCd)t). Sulfon-ation of 2-methyl-3,5-di-t-butylthiophene gives 2-methyl-5-t-butylthiophene-3-sulfonic acid (63AHC(l)l). However, 2,5-di-r-butylthiophene is monosulfonated normally at the 3-position (63AHC(l)l) under forcing conditions 2-(-butylthiophene-3,5-disulfonic acid is obtained. 

Later also thiophene-2-sulfonyl chloride and thiophene-3-sulfonamide were synthesised in the laboratory of Victor Meier [146, 147]. 

In the solvolysis of thiophene-2-sulfonyl chloride in low polarity solvents,... 

The kinetics of the reaction of 5-substituted thiophene-2-sulfonyl chlorides with aniline in methanolic solution has been studied and has been demonstrated to be a second order process. 

Naphthyl)- and 2-thiophene sulfonamide analogues have also been prepared by reacting the corresponding arylsulfonyl chloride with a amino pyrimidine derivative (2) as illustrated in Eq. 2 using 2-thiophene sulfonyl chloride. 

Rejerences. The procedure above is a modification of the method of Steinkopf and Hopner, Ann., 501, 174 (1933), adapted by R. Smith, Socony-Vacuum Laboratories. Burton and Davy, J. Chem. Soc., 1948, 525, obtained a 50% yield of 2-thiophene-sulfonyl chloride by Steinkopf and Hopner s method. 

Reaction with 4-toluenesulphonyl chloride occurred in a similar manner, leading to formation of (70). The use of alternative sulfonyl chlorides, for example methane sulfonyl chloride or 2-thiophene sulfonyl chloride resulted, however, in decomposition of the molecule. 

Thiophene-2-carboxanilide and its /7-chloro and p-bromo derivatives reacted smoothly with excess chlorosulfonic acid (six equivalents) at 40 C to yield the corresponding sulfonyl chlorides 526-528. The thiophene sulfonyl chlorides were used to prepare the corresponding sulfonylamino acids, methyl esters and hydrazides. The sulfonylamino acids were also coupled with the appropriate amino acid methyl esters to form the sulfonamino dipeptide methyl esters. ... 

Thiophene-2-sulfonic acid is a strong acid, similar to benzenesulfonic acid. It forms a sulfonyl chloride with phosphoryl chloride which on reduction with zinc yields thiophene-2-sulfinic acid. 

Styryl sulfonyl chloride Friedel-Crafts cyclization benzo[h]thiophenes from, 4, 873 Succinic anhydrides polymers, I, 277 mass spectrometry, 4, 585 structure, 4, 552... 

Sulfonation with sulfur trioxide, pyridine sulfur trioxide, pyridine bis-sulfur trioxide, and dioxane sulfur trioxide, which are useful sul-fonating agents for acidophobic substances, have been applied to the thiophene seriesd At room temperature the 2-monosulfonic acid (isolated as the barium salt) is obtained in 86% yield. Higher temperatures lead to a disulfonic acid. However, sulfonation with chloro-sulfonic acid appears to be more convenient,as the sulfonyl chloride obtained can be used directly for the preparation of derivatives. 

Finally, certain 3-substituted compounds can be prepared by utilizing the - meta) directing powet (cf. Section IV,B) of some groups in the 2-position which afterward can be removed. 3-Nitrothiophene is prepared by nitration of 2-thiophenesulfonyl chloride and by removal of the sulfonic acid group of the 4-nitro-2-sulfonyl chloride formed with superheated steam. Another approach to 3-nitrothio-phene is to nitrate 2-cyanothiophene, separate the 4-nitro-2-cyano-thiophene from the 5-isomer, hydrolyze, and decarboxylate. A final method of preparation of 3-nitrothiophene is by simultaneous de-bromination and decarboxylation of 5-bromo-4-nitro-2-thiophene-carboxylic acid obtained through the nitration of methyl 5-bromo-2-thiophenecarboxylate. 

Thiophenethiols are prepared by reduction of the sulfonyl chlorides or, more conveniently, by the reaction of Grignard rea-gents or thienyllithium compounds with sulfur. They have also been obtained by cleavage or thienyl alkyl sulfides with sodium in liquid ammonia. 3-Thiophenethiol is a by-product in the commercial thiophene synthesis. Thiophenethiols have recently also been prepared by a synthesis involving Friedel-Crafts reaction of 2,4-dinitrobenzenesulfenyl chloride with thiophenes, followed by basic cleavage of the resulting sulfide. ... 

Replacement of a benzene ring by its isostere, thiophene, is one of the more venerable practices in medicinal chemistry. Application of this stratagem to the NSAID piroxicam, gives tenoxicam, 136, a drug with substantially the same activity, nie synthesis of this compound starts by a multi-step conversion of hydroxy thiophene carboxylic ester 130, to the sulfonyl chloride 133. Reaction of that with N-methylglycinc ethyl ester, gives the sulfonamide 134. Base-catalyzed Claisen type condensation serves to cyclize that intermediate to the p-keto ester 135 (shown as the enol tautomer). The final product tenoxicam (136) is obtained by heating the ester with 2-aminopyridine [22]. 

Thiomethyl iminoether formation, 289 Thiophene formation, cycloaddition, thioglycolate, 583 Thiophenodiazepine formation, 622 Thiophenol formation, 527 sulfonyl chloride, 527 Thiourea formation... 

Benzo[6]thiophene 1,1-dioxides have been made by cyclization procedures (Section 3.15.3.1.7). Homologs of acetophenone cyclize on treatment with chlorosulfonic acid to give 2-substituted 3-chlorobenzo[6]thiophene 1,1-dioxides (equation 86). Similarly 1,1-diaryl-1-propenes in concentrated sulfuric acid gave 2-methyl-3-arylbenzo[6]thiophene 1,1-dioxides (65JOC2840). Friedel-Crafts cyclization of l,l-diphenylethylene-2-sulfonyl chloride gave 3-phenylbenzo[6]thiophene 1,1-dioxide (equation 87) (59JA2000). Treatment of various biphenyl derivatives with fuming sulfuric acid forms the dibenzothiophene 5,5-dioxides (Section 3.15.3.1.7). 

Sulfonation of benzo[6 ]thiophene with concentrated sulfuric acid in acetic anhydride at 20 °C gives a mixture which is chiefly the 3-sulfonic acid, with some 2-isomer and 3-acetylbenzo[6 Jthiophene (70AHC(i)l77). Chlorosulfonation of 2- or 3-methyl-benzo[6 Jthiophene gives the corresponding 3- or 2-sulfonyl chloride in satisfactory yield. The various available 4-, 5-, 6- and 7-mercaptobenzothiophenes or sulfides (Section 3.15.9.5.2) can be oxidized to sulfonic acids or sulfones by conventional means. 

The 4H NMR spectra of some methyl-,79-83 halo-,81 mercapto-,84 nitro-,84 and methoxybenzo[6]thiophenes,85 and of some sulfonic acids, sulfonyl chlorides, and sulfonate esters86 have been recorded. Two groups of workers87,88 have independently studied the 4H NMR spectra of a range of benzo[6]thiophene derivatives in an attempt to correlate the chemical shifts of the protons with the substituents. Such a correlation helps to assign structures to new benzo[6]thiophene derivatives, and it also throws light on the influence of substituents on the NMR parameters of heteroaromatic systems in general. 

There is surprisingly little reliable information on the sulfonation of benzo[6]thiophene or its derivatives. Benzo[6]thiophene is more readily sulfonated than naphthalene.699 Reaction with concentrated sulfuric acid at 80° gives a mixture of mono-, di-, and trisulfonic acids, reaction with 70% sulfuric acid at 80° gives a monosulfonic acid,699 and reaction with 18% oleum gives a disulfonic acid 86 in each case the orientation of the products is unknown. Treatment of benzo[6]thiophene with concentrated sulfuric acid in acetic anhydride at 20° gives 3-acetylbenzo[6]thiophene (ca. 10%) and a sulfonation product (isolated as the potassium salt), which was believed to be the 3-sulfonic acid.660 Recently, the sulfonation product has been shown to contain the 2- (8%) and 3-isomer (92%), by conversion into the sulfonyl chlorides and reduction to a separable mixture of 2- and 3-mercaptobenzo[6]thiophene.84... 

Benzo[6]thiophene sulfonic acids (isolated as the potassium salts) may be converted into the sulfonyl chloride, and then into the corresponding sulfonamide,660 sulfanilide,660 sulfonate ester,86 or thiol.84 Sulfonyl chlorides are hydrolyzed by boiling water to the corresponding sulfonic acid.660... 

Carboxylic acids, acyl chlorides, and sulfonyl chlorides used for deri-vatization of 4-aminophenylalanine and >-4-am i n op h e ny I a I a n i n e are as follows 5-hydantoinacetic acid, / ran, v - 4 - co t i n i n ec a r b o xy I i c acid, isonicotinic acid, 3-pyridinepropionic acid, 4-hydroxyphenylacetic acid, 2-butynoic acid, 2-pyrazinecarboxylic acid, cyclopropanecarboxylic acid, 3-hydroxy-2-qui-noxaline carboxylic acid, 5-bromovaleric acid, propargyl chloroformate, 3,4-dimethoxybenzoyl chloride, 2-thiophenesulfonyl chloride, 3-thiophene-carboxylic acid, 2-thiophenecarboxylic acid, 2-methylbutyric acid, 2-thio-pheneacetyl chloride, benzoic acid, furylacrylic acid, 4-nitrophenyl acetic acid, 2,5-dimethoxyphenylacetic acid, p-toluenesulfonyl chloride, 4-(di-methylamino)phenylacetic acid, 3-indolepropionic acid, phenoxyacetic acid, 3-(dimethylamino)benzoic acid, cyclohexanecarboxylic acid, naphtha-lenesulfonyl chloride, 4-bromophenylacetic acid, 4-bromobenzoic acid, 2-phenoxybutyric acid, 3,4-dichlorophenylacetic acid, (l-naphthoxy)acetic acid. 

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