Benzenesulfonic Acid Derivatives

BENZENESULFONIC ACID DERIVATIVES As has been discussed previously, substituted -alkylbenzene-sulfonylureas often possess the property of releasing bound insulin, thus sparing the requirement for insulin injections in adult-onset diabetes. A pyrimidine moiety, interestingly, can serve as a surrogate for the urea function. 

A related agent, g1 icetanile sodium (42), is made b / a variant of this process. Methyl phenyl acetate is reacted with chlorosulfonic acid to give 38, which itself readily reacts with aminopyrimidine derivative 39 to give sulfonamide Saponification to acid 4 is followed by conversion to the acid chloride and amide formation with 5-chloro-2-methoxyaniline to complete the synthesis of the hypoglycemic agent glicetanile (42).  

Perhaps surprisingly, the p-methyl benzenesulfonylurea analogue called tosi fen (45), which is structurally rather close to the oral hypoglycemic agents, is an anti anginal agent 

Several obvious variants exist. Tolbutamide, the prototypic drug, has some anti arrhythmic activity by an unknown mechanism. his side effect has become the principal action with tosifen, which itself does not in turn significantly lower blood 

Koelling, H. Thomas, A. Widdig, and H. Wollwever, German Offen. DE2,423,679 (1975) Chem. Abstr., 84, 73949k (1976). 

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A Methylamino)phenol. This derivative (15) is easily soluble ia ethyl acetate, ethanol, diethyl ether, and benzene. It is also soluble ia hot water, but only spatingly soluble ia cold water. Industrial synthesis is by heating 3-(A/-methylamino)benzenesulfonic acid with sodium hydroxide at 200—220°C (179) or by the reaction of resorciaol with methylamiae ia the presence of aqueous phosphoric acid at 200°C (180). 

A A Diethylamino)phenol. This derivative (16) forms rhombic bipyramidal crystals. Industrial synthesis is analogous to the previously described synthesis of 3-(/V,/V-dimethy1amino)pheno1 from resorciaol and diethylamiae, by reaction of 3-(Ai,A/-diethylamiQo)benzenesulfonic acid with sodium hydroxide, or by alkylation of 3-amiaophenol hydrochloride with ethanol. 

In the Chemical Abstracts method (also accepted by IUPAC Rule C-912), the naming of monoazo compounds with radicals R derived from two identical parent hydrocarbon hydrides is the same as mentioned above (for an exception see C-912.2). If the azo group links groups that are different when unsubstituted (R-N2-R ), a parent molecule RH is treated as substituted by R -N2- (Rule C-912.4) thus, 1.8 is called 4-(2-hydroxy-l-naphthylazo)benzenesulfonic acid or 4-(2-hydroxy-... 

Further development in the area of alternate value-added products for improving economics included other oxygenated sulfur compounds [246,247], This invention included alkylated 2-(2-hydroxyphenyl) benzenesulfinic acid and 2-(2-hydroxyphenyl)-benzenesulfonic acid compounds and compositions which consist essentially of 2-(2-hydroxyphenyl) benzenesulfinic acid, 2-(2-hydroxyphenyl)-benzenesulfonic acid and/or substituted derivatives. The compositions are useful as hydrotropes and are also of use as, or as starting materials for, surfactants, and as starting materials for the synthesis of other useful chemicals such as, polymers and resins, solvents, adhesives, and biocides. 

In 2006, Akiyama and coworkers established an asymmetric Brpnsted acid-catalyzed aza-Diels-Alder reaction (Scheme 36) [59]. Chiral BINOL phosphate (R)-3o (5 mol%, R = 2,4,6- Pr3-CgH2) bearing 2,4,6-triisopropylphenyl groups mediated the cycloaddition of aldimines 94 derived from 2-amino-4-methylphenol with Danishefsky s diene 95 in the presence of 1.2 equivalents of acetic acid. Piperidinones 96 were obtained in good yields (72 to >99%) and enantioselectivi-ties (76-91% ee). While the addition of acetic acid (pK= 4.8) improved both the reactivity and the selectivity, the use of benzenesulfonic acid (pK= -6.5) as an additive increased the yield, but decreased the enantioselectivity. A strong achiral Brpnsted acid apparently competes with chiral phosphoric acid 3o for the activation of imine 94 and catalyzes a nonasymmetric hetero-Diels-Alder reaction. The role of acetic acid remains unclear. 

Benzenesulfonic acid and derivs 2 B61—B63 azidobenzenesulfonic acid 2 B62 m-benzenedisulfonyl diazide 2 B62 benzenesulfonic acid azoacetylhydrazide 2 B62... 

No description of higher nitrocompds cou. d be found in the literature (See also Benzenesulfenic and Benzenesulfonic Acids and Derivatives)... 

Benzenesulfonic Acid (called Benzolsulfonsaure in Ger), C6H6.S03H mw 158.18 solid, when an-hyd, mp 55-6°. It forms numerous salts and other derivs, some of which are expl. The prepn and props are given in Beil 11,26-9,(18-20) [9-11] This compd can cause serious local toxicity to skin and mucous membranes, as reported by Sax (1957),P 347... 

Formation of quinuclidine-3-carboxylic acid derivatives (68) from these reactions was conclusive proof of saponification of the ethoxy-carbonyl group at position 2 of the diester (61). A similar reaction takes place with diethyl quinuclidine-2,3-dicarboxylate.100 This is in agreement with the known principle of easier saponification of a- than j8-amino acid esters. Some 3-(j8-acyloxyethyl)-2-diethylaminomethyl-quinuclidines (69, 70)123 on distillation at atmospheric pressure cyclize with loss of ester and formation of a new tricyclic system, quinuclidino[2,3-c]piperidine (72). The same reaction takes place by heating the corresponding amino alcohol (71) with phthalic anhydride in the presence of benzenesulfonic acid.123... 

Mesylates are used for Ni-catalysed reactions. Arenediazodium salts 2 are very reactive pseudohalides undergoing facile oxidative addition to Pd(0). They are more easily available than aryl iodides or triflates. Also, acyl (aroyl) halides 4 and aroyl anhydrides 5 behave as pseudohalides after decarbonylation under certain conditions. Sulfonyl chlorides 6 react with evolution of SO2. Allylic halides are reactive, but their reactions via 7t-allyl complexes are treated in Chapter 4. Based on the reactions of those pseudohalides, several benzene derivatives such as aniline, phenol, benzoic acid and benzenesulfonic acid can be used for the reaction, in addition to phenyl halides. In Scheme 3.1, reactions of benzene as a parent ring compound are summarized. Needless to say, the reactions can be extended to various aromatic compounds including heteroaromatic compounds whenever their halides and pseudohalides are available. 

NX - - BENZENESULFONIC ACID, ALKYL deriv. and TALLOW ALKYL ETHOXYLATE SULFATE... 

Sulfur compounds I, II and IV, methyl sulfonic acid, ethylsulfonic acid and benzenesulfonic acid could have been derived from a number of precursors in the parent coal samples. Firstly, mercaptans and thiols will form sulfonic acids when oxidized with peroxides. However, the presence of methylmercaptan, ethylmercaptan and benzenethiol in an exhaustively extracted coal sample is highly unlikely and we believe that the sulfonic acids did not arise from these compounds. In addition, there is a possibility that these sulfonic acids may have come from pendant or terminal thioether groups. 

The sulfoxidation of benzene (Table 4, entry 38) yields benzenesulfonic acids and the respective derivatives. The electrophilic aromatic substitution reaction gives high yields and aqueous sulfuric acid or oleum is used for the sulfonation reaction, which is performed in cascades of reactor vessels. 

Methylation of 7-amino-l,2,3-triazolo[4,5-d]pyrimidine (8-azaadenine) (140) with dimethyl sulfate afforded the N-3 and N-9 methylated isomers 141 and 142, respectively, which upon further methylation with methyl iodide or benzenesulfonic acid methyl ester gave 3,7- and l,9-dimethyl-8-azaadeninium salts 144 and 145, respectively. Thermal decomposition of the dimethyl derivatives led to a transmethylation to give 6-methylamino-9-methyl-8-azapurine (143), whose methylation afforded 1- and 7-methyl-6-methylamino-9-methyl-8-azapurinium salts 146 and 147 (80ZOR2204) (Scheme 28). 

Both the sulfonic acid (-SO3H) and the carboxylic acid (-CO,H) groups are encountered in aromatic molecules. Introduction of one sulfonic acid group into the benzene ring gives benzenesulfonic acid (1), derivatives of which are named as the substituted benzenesulfonic acid. The corresponding carboxylic acid is benzoic acid (2). 

Although sulfonation resembles nitration and halogenation in many respects, there are certain important differences. The two most noticeable of these differences are the reversibility of sulfonation processes and the striking sensitivity of orientation to changes in the reaction temperature. Amino derivatives offer a further complication in that considerable amounts of ortho and para derivatives are often obtained. Thus at low temperatures, aniline gives a mixture of 0, m, and p-amino-benzenesulfonic acid,48 whereas dimethylaniline gives an almost equal... 

A number of substituted benzenesulfonic acid esters and p-chlorophenoxy-isobutyric acid esters produced hypolipidemic activity.35 Among a series of p-alkoxybenzoic acids, enhanced hypotriglyceridemic and hypocholesterol-emic activity was observed with oximino- (14) and chloro- (15) substituents.98 Hypocholesterolemia was observed after the administration of 16 to rats.97 Tetronic 701, a polymeric surfactant, also lowered serum cholesterol the tetrabenzoate of Tetronic 701 is of particular interest, since it produced comparatively less growth depression.98 Two linoleamide derivatives, (-)N-fa-phenyl-B-(p-tolyl)ethylllinoleamide (PTLA) and N-(a-methyl-benzoyl)linoleamide, suppressed serum and liver cholesterol levels in rats and inhibited cholesterol absorption b interfering with the hydrolysis of cholesteryl esters in the intestine.99 101... 

Lindner, O. Rodefeld, L. Benzenesulfonic acids and their derivatives. In UUmanns Encyclopedia of Industrial Chemistry] John Wiley and Sons New York, 2002. 

TABLE VIII. Derivatives of Benzenesulfonic Acid and of Phenol... 

Monosubstituted benzenes are named as derivatives of benzene or by common names such as toluene, benzaldehyde, benzoic acid, benzenesulfonic acid, phenol, and aniline. 

The aromatic chemical shifts of the sulfonic acid salts are similar to those of the parent acids. The shifts of benzenesulfonic acid, sodium salt are listed below followed by those of several para substituted derivatives... 

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