Diazonium sulfonyl chloride

Inclusion of a para acetyl group requires a somewhat different approach to the preparation of these compounds. Reaction of the diazonium salt from p-aminoacetophenone with sulfur dioxide affords the sulfonyl chloride, 203 this is then converted to the sulfonamide, 204, Elaboration via the carbamate with cyclohexyl-amine affords acetohexamide (205). ... 

Diazonium salts can be converted to sulfonyl chlorides by treatment with sulfur dioxide in the presence of cupric chloride. The use of FeS04 and copper metal instead of CUCI2 gives sulfinic acids (ArS02H). See also 13-18. 

This reactivity enables t/tro-substitution to be carried out at a specific position in the ring, irrespective of the presence of other contra-directing groups, and it allows the reaction to be carried out under mild conditions, or with weak electrophiles such as diazonium ions.2 Recent additions to the extensive list of electrophiles that have been used are toluene />-sulfonylisocyanate and ethoxycarbonyl isocyanate (Equation (53)),176 sulfonyl chloride,177 arene178 and silane sulfonyl chlorides,179 and dichloromethyl methyl ether (Equation (54)).1... 

Chlorobenzenesulfonamide can be prepared from -chloroaniline by diazotization and treatment of the resulting diazonium salt with sulfur dioxide and hydrochloric acid in the presence of cuprous or cupric chloride to yield the sulfonyl chloride (Ref. 4) which is converted to the sulfonamide with ammonia. 

More abundant are reductions with sodium sulfite which is applied in aqueous solutions (solubility 24%). Its specialties are reduction of peroxides to alcohols [257], of sulfonyl chlorides to sulfinic acids [252], of aromatic diazonium compounds to hydrazines [253], and partial reduction of geminal polyhalides [254] Procedure 43, p. 216). 

Amino-5-chloro-2-cyclohexylisoindolin-l-one (42.5 g) was dissolved in concentrated hydrochloric acid (425 ml) and the solution diazotized by the addition of sodium nitrite (21.25 g) in water (125 ml). The resulting diazonium salt solution was added to a solution of liquid sulfur dioxide (93 ml) in glacial acetic acid (243 ml) containing cuprous chloride (2.25 g). A yellow solid was precipitated this was filtered off, washed, dried and recrystallized from benzene to give 5-chloro-2-cyclohexylisoindolin-l-one-6-sulfonyl chloride (45 g, 80%) as a cream solid, MP 171°C to 174°C. 

Diazonium salts can be converted to sulfonyl chlorides by treatment with sulfur... 

In the laboratory of R. Bihovsky, a series of peptide mimetic aldehyde inhibitors of calpain I was prepared in which the P2 and P3 amino acids were replaced with substituted 3,4-dihydro-1,2-benzothiazine-3-carboxylate-1,1-dioxides. The synthesis began with the diazotization of the substituted aniline substrate using sodium nitrite and hydrochloric acid. The aqueous solution of the corresponding diazonium chloride product was added dropwise to the solution of acrylonitrile in a water-acetone mixture, which contained catalytic amounts of copper(ll) chloride. This Meerwein arylation step afforded the chloronitrile derivative, which was subjected to sulfonation with chlorosulfonic acid, and the resulting sulfonyl chloride was treated with the solution of ammonia in dioxane to give the desired 3,4-dihydro-1,2-benzothiazine-2-carboxamide. 

The preparation of all four mononitro aromatic derivatives of 1,2-benzisothiazol-3-one S,S-dioxide was reported. As an example, the preparation of the 5-nitrosaccharin 314 Method 0) from nitro-lH-benzo[d][l,3] oxazine-2,4-dione 312 is outlined in the Scheme 76. Starting from 312, which was treated with K2CO3 in MeOH, the methyl 2-amino-5-nitrobenzoate 313 was formed. The amino group was transformed into the diazonium salt (NaN02 in AcOH/HCl). Its reaction with CuCh and sulphur dioxide afforded the corresponding sulfonyl chloride, which was added to cold concentrated ammonium hydroxide and 314 was isolated in 74% yield [lOOj. 

Sianesi and co-workers39,40 utilized o-aminophenylacetonitrile (48) as starting material for a four-step synthesis of compounds related to 47. Thus, diazotization of aniline 48 and treatment of the diazonium salt with S02/Cu2Cl2 yielded the sulfonyl chloride 49 (Eq. 11). Treatment of 49 with primary amines produced the corresponding sulfonamides 50 which were cyclized by sulfuric acid to the 3-imino compounds 51. Finally, aqueous hydrolysis of the imine 51 produced the desired 1,2-benzothiazin-3 (2H)-one 1,1-dioxides (47) (R = H, Et, and Ph) (Eq. 11). 

An amino group can also be acylated <84JHC697, 86JHC935) it reacts with sulfonyl chlorides and aryl isocyanates <86JHC935>, and also with nitrous acid to give, via the diazonium salt (281), either the triazinone by reaction with water or the chloro-triazine by reaction with chloride ions (Scheme 50). Nitrosation of 3-amino-1,2,4-triazine 2-oxides (282) and subsequent thermolysis of the diazonium tetrafluoroborate salts (283) afforded 3-fluoro-1,2,4-triazine 2-oxides (284) (Scheme 51). In one instance the diazonium tetrafluoroborate was isolated <85H(23)1969>. 

Several reactive pseudohalides are available for catalytic reactions. Diazonium salts 2 derived from anilines, and phenyl triflates 3 and nonaflates (nonafluorobu-tanesulfonates) derived from phenols are highly reactive substrates. In addition, acyl chlorides 4, anhydrides 5, and sulfonyl chlorides 6 are also used. 

Bridged Sulfonamides. The most convenient syntheses of 3-bridged pyrazole sulfonamides utilizes either a mercapto group or amine functionality as a handle to prepare the requisite sulfonamide. For example, one can prepare a pyrazole sulfonamide with many of the required substituents by the scheme depicted below. Condensation of methyl hydrazine with chloroacrylonitrile yields N-methyl-3-aminopyrazole 58 (12-13). The amine is protected by acylation. Chlorination at the 4 position with sulfuryl chloride, followed by deprotection provides 3-amino-4-chloropyrazole 59. The sulfonamide 60 is prepared by decomposition of the diazonium salt of 59 in SO2/CUCI followed by amination of the resulting sulfonyl chloride. 

The chlorosulfonation of benzenesulfonamides is employed in the synthesis of substituted benzenedisulfonamides 376 used as vasodilatory drugs. The chlorosulfonation was achieved indirectly by diazotization of the appropriate sulfanilamide 377, followed by treatment of the diazonium complex with acetic acid, sulfur dioxide and copper(ii) chloride as described by Holland et al In the final step, the sulfonyl chloride was condensed with the appropriate amine to give the disulfonamide 376 (Scheme 12). 

Diazotization of the atyl amine with NaN02 and HCl followed by treatment the diazonium salt with excess sulfur dioxide in acetic acid in the presence of a copper catalyst provides the sulfonyl chloride (Scheme 13.9). ... 

The water content in the system must be minimised in order to avoid hydrolysis of the sulfonyl chloride. Notably, special care should be taken in the handling of diazonium salts, as they are often heat, shock, or friction sensitive. In addition, the diazonium intermediate is temperature sensitive, in some cases decomposing at temperatures as low as 5 °C. An alternative aqueous procedure has been developed which allows the resultant sulfonyl chloride to be protected from hydrolysis by preeipitation of the product from the reaction mixture, using thionyl chloride as the sulfur dioxide equivalent (Scheme 13.10). ... 

In Pschorr reactions involving anilides, amido groups must be protected to avoid the formation of triazinones122 iV-alkylation has commonly been employed, but the resulting iV-alkylphenanthridones are difficult to dealkylate. Similarly, protection by AT-alkylation has been employed in the case of the benzylamine (104 (R = Me).138 In a procedure designed to circumvent this difficulty, the N-sulfonylated diazonium chlorides, e.g., 104a-c, are decomposed catalytically acid hydrolysis, followed by oxidation, of the 5,6-dihydro derivative... 

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