Benzenesulfonyl chloride sulfonylation with

In recent years, a variety of aryl boronic acids are commercially available, albeit in some cases they may be expensive for large scale purposes. During our work in the mid-1990 s boronic acid (II) was not commercially available and so two different protocols were used to prepare this acid. The first approach involved the transmetallation with n-butyl lithium of aryl bromide (I) and trapping the lithio species generated with trialkyl borate followed by an acid quench. Aryl bromide (I) is easily prepared by reaction of o-bromobenzenesulfonyl chloride with 2-propanol in the presence of pyridine as a base. The second approach was a directed metallation of isopropyl ester of benzene sulfonic acid (VII), to generate the same lithio species and reaction with trialkyl borate. The sulfonyl ester is prepared by reaction of 2-propanol with benzenesulfonyl chloride. From a long-term strategy the latter approach is... 

Rogne (1970) has measured the reactivity of some of the same nucleophiles toward benzenesulfonyl chloride in water at 25°. When log km for reaction of these nucleophiles with PhSOjCl is plotted vs. the log values for the same nucleophiles from Table 10, one obtains a good straight line relationship with a slope of about 0.8. This shows that the reactivity pattern observed with PhSOjSOjPh and shown in Table 10 is representative of what will be observed generally in nucleophilic substitution at the sulfonyl sulfur of reactive sulfonyl substrates. 

In what was intended as another experimental probe to ascertain whether a concerted or stepwise mechanism was involved in substitution reactions of arenesulfonyl chlorides, Rogne (1975) measured the enthalpies of transfer from propanol to acetonitrile for the transition states, SAH, for the reaction of imidazole with (a) benzoyl chloride and (b) benzenesulfonyl chloride. He found that SAH was considerably more negative for the reaction involving the sulfonyl chloride than for the one involving benzoyl chloride. This means that the transition state for attack of imidazole on benzenesulfonyl chloride is considerably better solvated by acetonitrile relative to its solvation by propanol... 

In order to access the C-2 position, indirect methods of reaction are used, and a common procedure is to A-sulfonate indole with sodium hydride and benzenesulfonyl chloride and then to treat the derived sulfonate with butyllithium. C-2 deprotonation and lithiation occur (facilitated by chelation to the sulfonyl group) and the intermediate, without isolation, can then be reacted with a wide range of electrophiles at this site. Finally, the sulfonyl group can be hydrolysed off in a separate step to form the desired product (Scheme 7.10). 

A Indole, when treated with one equivalent of sodaniide and then with benzenesulfonyl chloride, gives l- pheny sutronyl)indole. The A -sulfonyl substituent activates the H-2 to deprotonation by butyl-lithium and stabilizes the lithium derivative by chelation. This oriho lithiation process facilitates subsequent acetylation at this site by acetyl chloride, affording 2-acetyl-l-(phenylsulfonyl)indole (Scheme 7,11). 

Sulfonylations of anions formed by deprotonation of azinones are not described in previous editions <1984CHEC(2)1, 1996CHEC-II(6)1>. 4,5-Dichloropyridazin-3(2//)-one is sulfonylated at N-2 with several benzenesulfonyl chlorides in the presence of a base <2002JHC203>. Reactions of the resulting compounds with amines yield sulfonamides (see Section 8.01.8.5). 

The combinatorial reactions chosen for the novel amines were amide bond formation and sulfonamide formation. The novel carboxylic acids were derivatized to simple amides. For the amine reactions, we chose two simple carboxylic acids (propionic acid and benzoic acid) and two simple sulfonyl chlorides (methyl-sulfonyl chloride and benzenesulfonyl chloride) as the capping groups. Propyl amine and benzylamine were chosen as the capping groups to react with the novel carboxylic acids. Because only one reactant will be variable, these combinatorial libraries were essentially 1 x N libraries, where the one reactant was a simple reactant and the N component is the novel amines or acids. 

Miller and Walling1 6 have shown that both bromine and sulfonyl chloride groups can be displaced during the photochemical reaction of chlorine with p-bromobenzenesulfonyl chloride and that a similar displacement of the sulfonyl group of benzenesulfonyl chloride occurs to give chlorobenzene. 

N-Sulfonylation of the alkali metal salts or under phase-transfer catalytic conditions has been extensively reported (e.g. 68TL1721,81TL4899,81TL4901,81S460), although an unprecedented preferential sulfonylation at the 4-position has been observed in the phase-transfer catalyzed reaction of 2-(2-pyridyl)indole with benzenesulfonyl chloride (79JHC1631). 

Sulfonylations under Friedel-Crafts conditions (A1C13) are known in the thiophene series. Thus 2,5-dichlorothiophene with benzenesulfonyl chloride gives phenyl 2,5-dichloro-3-thienyl sulfone (63AHC(1)1). 

Sulfonic acids are converted to the corresponding acid halides in much the same way as carboxylic acids. Thionyl chloride is the best reagent for the preparation of methanesulfonyl chloride (83%). By heating with a large excess of thionyl chloride, however, p-toluenesulfonic acid is converted into its anhydride (87%). Benzenesulfonyl chloride is made in 80% yield by the action of either phosphorus pentachloride or phosphorus oxychloride at 180° on sodium benzenesulfonate. Chlorosulfonic and fluorosulfonic acids are used in the conversion of sodium p-chloro-benzenesulfonate to the corresponding sulfonyl halides (85 8S>%). ... 

Matsuura and co-workers (756) have reexamined the reactions of the A -oxides of 2,5-dimethylpyrazine and found that 2,5-dimethylpyrazine di-A -oxide (29) when heated with phosphoryl chloride at 160° gave 2,5-dichloro-3,6-dimethylpyrazine (6%) (30), 3-chloro-2,5-dimethylpyrazine 1-oxide (5%) (31), and 5-chloromethyl-2-methylpyrazine 1 -oxide (9%) (32). In addition small amounts of other chlorinated products, 3-chloro-2-chloromethyl-5-methylpyrazine (33) and 2,5-bischloromethyl-pyrazine (34), were identified. These authors also examined the action of p-tosyl chloride, methane sulfonyl chloride, and mixtures of phosphoryl chloride and concentrated sulfuric acid, but state that these did not give good results. Pyrazine 1-oxide and phosphoryl chloride have been shown to give 2reaction conditions it gave 2-chloropyrazine 1-oxide (757). Pyrazine 1,4-dioxide and benzenesulfonyl chloride also gave a low yield of 2-chloropyrazine 1-oxide (758). 

An alternate method of converting sulfonyl chlorides to sulfonyl fluorides has been reported by Sigler et al. (1966) in the synthesis of benzene sulfonylfluoride. Benzenesulfonyl chloride (18 g, 0.1 mole) was dissolved in 100 ml of acetone and then mixed vigorously at room temperature for 4 hr with 100 ml of aqueous 4 M potassium fluoride. On evaporation of the acetone, the pale yellow liquid product separates. It can be dried after dissolution in methylene chloride over anhydrous MgS04 and then distilled as a colorless oil (b.p. 63-67°C/6-7 mm). 

Sulfonyl halides (e.g. benzenesulfonyl chloride) form adducts (11) with acid amides in an equilibrium reaction. From these adducts or via adducts of this type 0-sulfonated lactim ethers, isonitriles, adenine, nitriles, amidines, amidinium salts and formic acid esters were prepared. The adducts from DMF and chlorosulfonamides (12) can be used to prepare amidines or amidrazones. A/-Chlorosulfonylcarboxylic acid amides yield nitriles on treatment with DMF or other tertiary amides, presumably via an acid amide sulfonyl chloride complex (13 equation 3). ... 

P-Chlornviny/sulfones. In the presence of copper(l) or copper(II) salts as catalysts, sulfonyl chlorides add to acetylenes to give /J-chlorovinyl sulfones No reaction takes place in the absence of catalysts. Acetonitrile or methylene chloride is used as solvent. A small amount of a quarternaiy ammonium chloride (e.g., tetraethylammonium chloride) is added to solubilize the copper salts. The reaction is carried out at reflux or, preferably, in a sealed tube. The reaction is stereoselective thus the reaction of benzene-sulfonyl chloride (2) with phenylacetylene (1) leads to two isomeric 2-benzenesulfonyl-1-chlorostyrenes (3) and (4). The main product (3) results from trans addition, the... 

Sulfonyl chlorides. Adams and Marvel prepared benzenesulfonyl chloride by heating sodium benzenesulfonate with PCI in an oil bath at 170-180° for 15 hrs. every 4 hrs. the flask was removed from the oil bath, stoppered, and shaken until the mass became pasty. The mixture was cooled, treated with ice and water, and 170-180°, 15 hra,. 

Methanesulfonyl chloride is the largest-volume alkanesulfonyl chloride. Benzenesulfonyl chloride is the only aromatic sulfonyl halide with significant commercial production, primarily as a feedstock for the manufacture of A-butyl benzenesulfonamide. All sulfonyl chlorides are poorly water soluble, which limits their hydrolysis except at elevated temperatures or in the presence of a homogenizing agent such as a cosolvent, surfactant or phase-transfer agent. 

FIGURE 9.16 Ammonia derivatization process involving benzene sulfonylation with benzenesulfonyl chloride and subsequent reaction with dimethylformamide dimethyl acetal to form benzesulfonyldimethyl-aminomethylene derivative. 

Two sterically hindered /V-sulfonylated aminobomeols 42 were prepared from camphorquinone 11 and used after esterification for the formation of enolates which are alkylated or oxidized diastereoselectively (Sections D.1.1.1.3.2., D. 1.5.2.1., D. 1.5.2.3. and D.4.I.). The synthesis of these auxiliaries involves the reaction of camphorquinone 11 with 3,5-dimethylaniline to give the mono-imine by reaction with the sterically less hindered carbonyl group, followed by reduction with boranate and reaction with benzenesulfonyl chloride to give the exo.exo-product. or initial reduction with zinc/potassium hydroxide, then sulfonylation, and finally reduction with boranate to give the endo,endo-isomer21. 

The target triazolo[l,5-c]pyrimidine sulfonamides 6 were prepared via coupling 7 with substituted benzenesulfonyl chlorides (Scheme 2). In these transformations, pyridine and a catalytic amount of dimethylsulfoxide (DMSO) were essential for the formation of 6. The reactive intermediate is believed to be the in situ generated sulhlimine 10 which allows for the relatively non-nucleophiKc amines to react with sulfonyl chlorides under mild conditions [7-8],... 

The tosylation of carbon can be accomplished using electron transfer conditions. Treatment of styrene and analogs with Copper(II) Chloride and tosyl chloride or Benzenesulfonyl Chloride results in a formal replacement of the vinyl proton by the sulfonyl moiety (eq 35). The intermediacy of a trans-(S-chloro sulfone has been demonstrated by H NMR. Treatment with base induced the elimination of HCl. A variety of other sulfonyl transfer reagents can be ertployed in the synthesis of isolated /3-chloro sulfones, with good results (60-97% yield) for a variety of alkenes (ethylene, 1-butene, 2-butene, 1-octene, acrylonitrile, methyl acrylate, and 1,3-butadiene). ... 

Several substituted benzene and pyridine sulfonyl chlorides from which to prepare sulfonamides have been investigated. However, with respect to crop selectivity, most interest has focused on 2,6-disubstituted benzenesulfonyl chlorides and 2,4-disubstituted pyridine-3-sulfonyl chlorides. A general method for the preparation of various benzene and pyridine sulfonyl chlorides is via ortho directed met-alation [32, 37]. The sulfonyl chlorides (17) can be prepared directly from the aryl lithium species by reacting with sulfur dioxide followed by sulfuryl chloride (Scheme 2.4.3). Alternatively, reaction of the aryl lithium species with a disulfide. 

Benzenesulfonyl chloride [98-09-9] M 176.6, m 14.5", b 120"/10mm, 251.2"/760mm(dec), d 4 1.384. Distil the sulfonyl chloride, preferably under a vacuum, then treat it with 3mole % each of toluene and AICI3, and allow it to stand overnight. The sulfonyl chloride is distilled off at 1mm pressitre and then carefully fractionally distilled at 10mm in an all-glass colurtm. [Adams Marvel Org Synth Coll Vol 184 1941, Jerrsen Brown J... 

The actual formation of hyperbranched material proceeds during the polymerization of 3,5-difiuoro-4 -hydroxydiphenyl sulfone in the presence of 3,4,5-trifluorophenylsulfonyl benzene or tris(3,4,5-trifiuorophenyl)phosphine oxide as a core molecule. Cyclic oligomers formed during this polymerization contribute to a low-molecular-weight polymer ranging from 3400 to 8400 Da. A triazin-based AB2 monomer has also been described [55]. This monomer is shown in Figure 7.11. A hyperbranched aromatic poly(ether sulfone) with sulfonyl chloride terminal groups has been prepared by the polycondensation of 4,4 -(m-phenylenedioxy)-bis-(benzenesulfonyl chloride). 

Numerous studies have been devoted to the addition of RSO2X to olefins. The propagation steps for these chain processes are shown in Scheme 13. The main factors controlling the reactivity of sulfonyl radicals are polar effects and the reversibility of the addition. Sulfonyl radicals exhibit an electrophilic character with respect to addition to olefins [98]. Evidence for the reversibility came early from the observation of the isomerization of cis- and rran -2-butenes during their copolymerization with sulfur dioxide and their Cu(I)-mediated reaction with benzenesulfonyl chloride [99]. Therefore, the chain transfer of alky] adduct radica]s has to compete effectively with -elimination of sulfonyl radicals (see Scheme 13). Selenosulfonates, sulfonyl halides, and sulfonyl cyanides are the most popular substrates that meet this property. 

Benzene (Table I, p. 165). Some of the factors involved in the industrial sulfonation of benzene have been discussed. In the small-scale, laboratory preparation, where the difference in cost between sulfuric acid and oleum is negligible, oleum is the preferred reagent. Benzene is added gradually to ice-cold sulfuric acid containing 5-8% of the anhydride the reaction is complete after ten to fifteen minutes. Benzensul-fonic acid is isolated readily as the sodium salt by the addition of the reaction mixture to a saturated sodium chloride solution. The reaction of benzene with chlorosulfonic acid is not used for the preparation of benzenesulfonic acid because, under conditions that limit the formation of the sulfonyl chloride, the acid is always accompanied by phenyl sulfone. Benzenesulfonyl chloride can be obtained in a yield of 75-77% by the addition of benzene to an excess of chlorosulfonic acid (room temperature). Fluorosulfonic acid reacts less vigorously the addi-... 

B. Benzenesulfonyl chloride (and other aryl sulfonyl chlorides) possess an advantage over the usual acyl chlorides of the acetyl or benzoyl type in that the sulfonyl derivatives of primary amines may be differentiated from the corresponding derivatives of secondary amines due to the solubility of the former in alkali. This reaction will be discussed further in Chapter XII in connection with its application to mixtures. 

Early studies of the kinetics of sulfonylation were carried out by Olivier, who examined the benzenesulfonylation of benzene, toluene and chlorobenzene using excess of benzenesulfonyl chloride as solvent and aluminium chloride catalyst. In all cases, the rate constants varied markedly with the concentration of the catalyst. Further kinetic studies of these sulfonylations showed that the order of reaction depends on the reactivity of the aromatic compound. The benzenesulfonylation of the more reactive substrate toluene showed second order kinetics, rate = k2[AlCl3][PhMe]. For benzene, the kinetic order is mixed, while for the less reactive chlorobenzene the rate was claimed to be three-halves, rate =... 

The properties of sulfonamides differ from those of amides. Because the sulfonyl group withdraws electrons more strongly than an acyl group, the N—H bond of the sulfonamide of a primary amine is acidic. Thus, reaction of a primary amine with benzenesulfonyl chloride yields a sulfonamide that is soluble in sodium hydroxide. 

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