text: it is well known in the art that various substituted anilines can be converted to the corresponding sulfonyl chlorides via a 2 - step process of diazotization and so 2 - cucl 2 decomposition : ## str3 ## wherein ar is phenyl or a substituted phenyl moiety . a detailed description of such a process by h . meerwein , g . dittmar , r . gollner , k . hafner , f . mensch an o . steinfort can be found in chemische berichte , vol . 90 , 1957 , pages 841 - 852 . however , it is not known in the art that a thiophenamine or a substituted thiophenamine can be converted to the corresponding thiophene sulfonyl chloride ( equation 3 ): ## str4 ## it has been found that such a conversion proceeds well when a thiophenamine of general formula ii is suspended in a mixture of excess concentrated hydrochloric acid ( also referred to herein as aqueous hydrochloric acid ) and a cosolvent selected from formic , acetic or propionic acid , optionally in the presence of a mineral - acid booster selected from hydrogen chloride , concentrated sulfuric acid or oleum , and the suspension is ( a ) contacted with an aqueous solution of sodium or potassium nitrite which produces a diazonium salt of general formula iii ; and ( b ) the diazonium salt iii so produced is contacted with cupric or cuprous chloride or bromide , in the presence of excess sulfur dioxide to give the desired thiophenesulfonyl chloride of general formula i . the procedure outlined above , however , requires that the concentrated hydrochloric acid be at least 35 weight percent for the attainment of highest yields and low levels of side products . when inexpensive , low - strength ( 28 - 32 weight percent ) hydrochloric acid and / or readily available water - wet thiophenamine are employed , the yields of thiophenesulfonyl chlorides decrease drastically . in addition , the sulfonyl chlorides have low purities , being contaminated with many side products among which the type represented by general formula iv predominates : ## str5 ## this type of impurity is very difficult to remove from the corresponding thiophenesulfonyl chloride i . in those instances , high yields of sulfonyl chloride i can be maintained and side - product formation can be minimized by the addition of hydrogen chloride , concentrated sulfuric acid or oleum to the diazotization mixture . most preferred in achieving higher yield and / or greater purity of products is the addition of concentrated sulfuric acid in the amount of 0 . 2 to 2 . 5 moles per mole of diazonium salt iii . the reactions of equation 3 comprising our improved process can preferably be carried out by the following procedure : to concentrated hydrochloric acid ( 35 - 38 weight percent ) is added glacial acetic acid as cosolvent . the amount of the former is selected to provide approximately 5 . 0 molar equivalents of hcl per mole of the substrate thiophenamine . the amount of cosolvent acetic acid is selected to provide a stirrable slurry of the substrate thiophenamine . if an inexpensive , lower - strength hydrochloric acid ( 28 - 32 weight percent ) and / or water wet thiophenamine are used , concentrated sulfuric acid is added at this stage for reason of the convenience of mixing sulfuric with hydrochloric acid and acetic acids . the amount of lower - strength hydrochloric acid is selected to provide from 2 to 4 molar equivalents of hcl per mole of thiophenamine . the amount of concentrated sulfuric acid varies from 0 . 2 to 2 . 5 moles per mole of thiophenamine , depending on the amount of water in a wet cake of thiophenamine , and the strength of concentrated hydrochloric acid . to the mixture of acids is gradually added the thiophenamine with some cooling . if a wet substrate is used , the water content of the wet cake can vary widely , e . g ., from 0 to 65 weight percent . the resulting slurry is cooled to 0 °- 7 ° c . and diazotized with one molar equivalent of sodium nitrite dissolved in water . in the course of diazotization , the starting material goes into solution . to the solution of the diazonium salt is added sulfur dioxide . its amount of the latter can vary from 1 . 2 to 5 molar equivalents for each molar equivalent of the diazonium salt . we preferably use about 3 molar equivalents of the sulfur dioxide . this is followed by the addition of cuprous chloride whose amount can vary from 3 to 6 mole percent . the mixture is warmed to room temperature and the decomposition of the diazonium salt is allowed to proceed to completion . alternatively , sulfur dioxide is dissolved in acetic acid containing cuprous chloride , to which is then added the soluton of the diazonium salt in a gradual fashion . the amount of acetic acid is selected to dissolve the required amount of sulfur dioxide . the reacting mixture is also allowed to decompose completely at room temperature . the resulting suspension of thiophenesulfonyl chloride is cooled and diluted with water . the product is recovered by filtration , washing with water and drying . the following table is a guide to the examples that follow . ______________________________________ extrathiophen - % hcl mineral % yield wt . % ex . amine strength acid . sup . a of product of iv . sup . b______________________________________1 dry 36 none 85 . 6 & lt ; 0 . 52 wet 37 hcl 79 . 0 & lt ; 1 . 03 wet 31 . 5 none 56 . 1 16 . 04 wet 31 . 5 h . sub . 2 so . sub . 4 82 . 3 0 . 125 dry 31 . 5 none 65 . 1 10 . 86 dry 31 . 5 h . sub . 2 so . sub . 4 82 . 7 0 . 26______________________________________ . sup . a dry hydrogen chloride , conc . h . sub . 2 so . sub . 4 , or oleum . . sup . b weight percent of the sideproduct iv in crude product . to a mixture of 385 g of concentrated ( 36 weight percent ) hydrochloric acid and 120 ml of glacial acetic acid were added 133 g of 92 . 4 % pure methyl 3 - aminothiophene - 2 - carboxylate while maintaining the internal temperature between 0 ° and 7 ° c . to the resulting slurry were slowly added 58 g of sodium nitrite dissolved in 77 ml of water at 0 ° to 7 ° c . a solution of the diazonium salt so obtained in one vessel was gradually transferred to a second vessel containing 310 ml of glacial acetic acid , 30 g of concentrated ( 36 weight percent ) hydrochloric acid , 4 . 8 g of cuprous chloride and 90 g of sulfur dioxide and maintained at 15 °- 17 ° c . while the transfer of the diazonium salt was in progress , additional 60 g of sulfur dioxide were slowly being charged subsurface into second vessel . the temperature of the reacting mixture was subsequently allowed to rise to 21 ° c . the mixture was stirred at room temperature until the evolution of nitrogen was complete . the title sulfonyl chloride was precipitated by the addition of 660 ml of water . it was then filtered , washed with water and dried in vacuo at 40 ° c . the crude product weighed 179 . 28 g and was found by high - pressure liquid chromatography to contain 164 . 94 g of pure sulfonyl chloride for a yield of 85 . 67 % of theory . the crude product contained less than 0 . 5 weight percent of the side - product of formula iv . to 49 ml of concentrated hydrochloric acid ( 36 - 38 %) and 20 ml of acetic acid was added a solution of 45 . 5 g . of a wet cake of methyl 3 - aminothiophene - 2 - carboxylate ( purity of 69 . 2 % and water content of 26 . 2 %) in 40 ml of glacial acetic acid at 0 °- 5 ° c . followed by a solution of 15 . 0 g of sodium nitrite in 21 . 6 ml of water also at 0 °- 5 ° c . to this mixture , kept at 0 °- 5 ° c . was slowly added 15 g of dry hydrogen chloride . after stirring the reaction mixture at 0 °- 5 ° c . for 30 minutes , 20 g of sulfur dioxide , 10 ml of acetic acid , and 1 . 0 g of cupric chloride dihydrate were added . the decomposition reaction was carried out at room temperature to completion . the product was precipitated by the addition of 200 ml of cold water at 0 °- 5 ° c ., the crystals were filtered , washed with water and dried in vacuo under nitrogen at 40 ° c . the crude product weighed 40 . 41 g and was found by a high - pressure liquid chromatography to contain 38 g of the title sulfonyl chloride which corresponded to a yield of 79 % of theory . the crude product also contained less than 1 wt . % of the side - product of formula iv . to 150 . 5 g of 31 . 5 % aqueous hydrochloric acid and 180 ml of glacial acetic acid was added gradually , with cooling , 0 . 40 mole of methyl 3 - aminothiophene - 2 - carboxylate as a wet cake containing 30 . 5 % of water . the resulting slurry was slowly diazotized at 0 °- 7 ° c . with 30 g of sodium nitrite dissolved in 43 ml of water . after completion of the addition of sodium nitrite the mixture was stirred at 0 °- 5 ° c . for an additional 20 - 30 minutes . to the diazonium salt solution were added 80 g of gaseous sulfur dioxide , 20 ml of glacial acetic acid , and 4 g of cupric chloride dihydrate . the mixture was stirred at 20 °- 25 ° c . until the evolution of nitrogen was complete . the reaction mixture was cooled to 0 °- 5 ° c ., 330 ml of water was gradually added and the precipitate was stirred at 0 °- 5 ° c . for 30 minutes . the solid product was filtered , with water , and dried in vacuo at 40 ° c . the crude material weighed 71 . 7 g and was found by high - pressure liquid chromatography to contain 53 . 9 g of sulfonyl chloride for a yield of 56 . 1 % of theory . the crude material also contained 16 . 0 wt . % of the side - product having formula iv . in the procedure of example 3 , 36 ml of concentrated sulfuric acid was added dropwise before the starting material at room temperature . the decomposition in the presence of sulfur dioxide was then carried out as described in example 3 . the procedure furnished 85 . 5 g of a crude product which by analysis contained 79 . 2 g of the title sulfonyl chloride for a yield of 82 . 3 % of theory the crude material also contained 0 . 12 wt . % of the side - product of formula iv . in the procedure of example 3 , 67 % of essentially dry methyl 3 - aminothiophene - 2 - carboxylate ( 94 . 7 % pure and containing 0 . 1 % of water ) was used in place of the wet cake . the experiment produced 79 . 0 g of a crude product which was found by high - pressure liquid chromatography to contain 62 . 7 g of the title sulfonylchloride . this corresponded to a yield of 65 . 1 % of theory . the crude material also contained 10 . 8 weight % of the side - product having formula iv . in the procedure of example 3 , 67 g of essentially dry methyl 3 - aminothiophene - 2 - carboxylate ( 94 . 7 % pure containing 0 . 1 % water ) was used in place of the wet cake . also , 26 ml of concentrated sulfuric acid were employed in the manner described in example 4 . the experiment produced 85 . 7 g of a crude product which was found by high - pressure liquid chromatography to contain 79 . 6 g of the title sulfonyl chloride . this corresponded to a yield of 82 . 7 % of theory . the crude material also contained 0 . 26 wt . % of the side - product having formula iv .