O-sulfobenzoic acid

Piroxicam Piroxicam, 1,1 -dioxid-4-hydroxy-2-methyl-iV-2-pyradyl-2//-1,2-benzothiazine-3-carboxamide (3.2.78), is synthesized from saccharin (3.2.70). Two methods for saccharin synthesis are described. It usually comes from toluene, which is sulfonated by chlorosulfonic acid, forming isomeric 4- and 2-toluenesulfonyl chlorides. The isomeric products are separated by freezing (chilling). The liquid part, 2-toluenesulfonyl chloride (3.2.68) is separated from the crystallized 4-toluenesulfochloride and reacted with ammonia, giving 2-toluenesul-fonylamide (3.2.69). Oxidation of the product with sodium permanganate or chromium (VI) oxide in sulfuric acid gives saccharin—o-sulfobenzoic acid imide (3.2.70) [123-126]. 

Benzoic sulfimide, benzosulfimide, benzoic sulfimide, o-sulfobenzimide, o-sulfobenzoic acid imide, saccharin, saccharin insoluble. 

The only practical methods for the preparation of o-chloro-benzoyl chloride to be found in the literature consist in the treatment of o-chlorobenzoic acid with phosphorus penta-chloride1 or thionyl chloride.2 It has, however, also been formed by distilling salicylic acid or its sodium salt with phosphorus pentachloride,3 and by heating the dichloride of o-sulfobenzoic acid.4... 

Acid hydrolysis of 67 back to 8 seems to require rather drastic conditions125 in keeping with the soft character127 of 67 as a base. Eventually 8 is hydrolyzed to the methylammonium salt of o-sulfobenzoic acid (52b).125 3-Alkylthiosaccharins (4) are hydrolyzed with acid to 52b and the thiol somewhat more readily.125... 

RCRA WASTE NUMBER U202 SACARINA SACCAHARIMIDE SACCHARINA SACCHARIN ACID SACCHARINE SACCHARINOL SACCHARINOSE SACCHAROL SAXIN SUCRE EDULCOR SUCRETTE o-SULFOBENZIMIDE o-SULFOBENZOIC ACID IMIDE 2-SULPHOBENZOIC IMIDE SYKOSE SYNCAL ZAHARINA... 

Benzisothiazolin-3-one 1,1-dioxide benzoic sulfimide benzosulfimide l,2-dihydro-2-ketobenzisosulfonazole 2,3-dihydro-3-oxobenzisosulfonazole E954 Garantose gluside Hermesetas sacarina saccharin insoluble o-sulfobenzimide o-sulfobenzoic acid imide. 

In many cases, particularly for aryl acid anhydrides, the sodium, ammonium, or potassium salt of the acid is heated with sufficient phosphorus oxychloride or thionyl chloride to convert half of the salt into the acid chloride. The latter reacts with the other half of the salt to give the anhydride. This method is used for the preparation of the anhydride of o-sulfobenzoic acid (see page 339). Finally, a few dicarboxylic acids, such as phthalic acid, which contain two carboxyl groups attached to adjacent carbon atoms, when heated above their melting point lose water and form the anhydride. 

F) Preparation of Sulfonphthaleins. The preparations described involve (1) hydrolysis of o-sulfobenzoic imide (saccharin) to the ammonium salt of o-sulfobenzoic acid (2) preparation of o-sulfo-benzoic anhydride (3) preparation of phenolsulfonphthalein (phenol red) (4) bromination of phenolsulfonphthalein to tetrabromo derivative (bromophenol blue) (5) preparation of o-cresolsulfon-phthalein (cresol red) (6) bromination of o-cresolsulfonphthalein to the dibromo derivative (bromocresol purple)The equations for the steps are ... 

Preparation, purity, and properties of the sulfonephthaleins. The preparation of the various sulfonephthaleins from o-sulfobenzoic acid, molten zinc chloride, and a phenol (which may be halogen substituted) has been described by Clark and Lubs. A. Cohen has reported his method of obtaining xylenolsulfone-phthalein, while a number of other valuable sulfonephthaleins have become available through the work of Barnett Cohen. ... 

The sodium salt of benzosulfimide, i.e., sodium saccharinate, the cyclic imide of o-sulfobenzoic acid, increases the molecular weight of the polymer. The mechanism is not explained. ... 

Saccharin insoluble Saccharum o-Sulfobenzimide o-Sulfobenzoic acid imide Ciassification Organic compd. o-toluene sulfonamide... 

Sulfide of sodium. See Sodium polysulfide Sulfinylbis (methane). See Dimethyl sulfoxide Sulfinyl chloride. SeeThionyl chloride Sulfiram. See Tetraethylthiuram sulfide Sulfisomezole. See Sulfamethoxazole Sulfite lignin. See Lignin sulfonate Sulfoacetic acid, 1-dodecyl ester, sodium salt Sulfoacetic acid dodecyl ester S-sodium salt. See Sodium lauryl sulfoacetate 2-Sulfoanthraquinone sodium salt. See Sodium 2-anthraquinone sulfonate Sulfobenzide. See Diphenyl sulfone o-Sulfobenzimide o-Sulfobenzoic acid imide. See Saccharin... 

Based on its availability and structural nature, investigation of the " dehydrating power of o-sulfobenzoic acid anhydride (I) was carried out The parent add may be readily available as an intermediate in the synthesis of saccharin (5). The cyclic nature of this anhydride along with its half sulfonic/ half benzoic composition hinted to us that it may prove to be a suitable compound for the present isocyanate technology. 

Table n. Conversion of Amines to Isocyanates Using o-Sulfobenzoic Acid Anhydride... 

The results for the reaction of triaminononane - tris carbamate with o-sulfobenzoic acid anhydride gave high yields of TTI (TAN triisocyanate)(7-5/ This isocyanate has been evaluated as a low viscosity, low vapor pressure crosslinldng agent in coating plications (P). 

A reasonable explanation for the formation of the substituted benzoic add anhydride from this reaction lies in competitive nucleophilic attack of generated caiboxylate on the o-sulfobenzoic acid anhydride as shown below 10) in equation 5. 

Independent conHimation of the plausibility of this reaction was demonstrated by the addition of an equal molar amount of the dianim of o-sulfobenzoic acid to the anhydride giving the same linear benzoic anhydride. This result points out that attack of the caiboxylate is competitive with carbamate attack on the cyclic anhydride. The generation of linear anhydride does not appear to affect the production of isocyanate. 

Thermal Reaction of Linear Anhydride The most desirable and simplest scenario for regeneration of o-sulfobenzoic add anhydride is the diermal cracking of the salt obtained, followed by thermal dehydration to the anhydride. Attempts to thermally effect this conversion have not been successful. Heating the linear anhydride in the solid state under a nitrogen purge generates one equivalent of o-sulfobenzoic acid anhydride and one equivalent of the sulfonate/benzoate as shown in equation 6. This is the reverse reaction of that observed for the formation of anhydride. 

Conversion of Linear Anhydride to o-Sulfobenzoic Add Anhydride Critical to the successful use of o-sulfobenzoic acid anhydride as a dehydrating agent for the production of isocyanates is the ability to recycle the anhydride. Since direct conversion from the isolated by-product appears to be unlikely, another pathway must be demonstrated. A reasonable route is shown below in Scheme m, and progress in each of the steps shown has been made. 

This route involves hydrolysis of the linear anhydride into the mono-triethylammonium salt followed by neutralization with caustic soda (or calcium hydroxide) to liberate the trielhylamine giving the sodium salt of o-sulfobenzoic acid. This salt is then converted to the free acid via protonadon by sulfuric add (or on an ion exchange column, regeneration of the ion exchange resin involves addition of a strong add such as sulfuric add). The free acid is then dehydrated thermally (driven by a physical removal of generated water) to o-sulfobenzoic add anhydride (JJ) as shown in equation 7. 

In situ trapping of isocyanate. The mild conditions of the "dehydration reaction using o-sulfobenzoic acid anhydride provided an opportunity to look at generating isocyanates in situ followed by immediate conversion of the isocyanate into urethane materials. This method may prove to be valuable for the generation of materials based on toxic, volatile isocyanates (i.e. methyl isocyanate). An example is shown below in Scheme V(/5) which shows the formation of 1-naphthyl N-methylcaibamate (common insecticide). 

Hexamethylene diiso anate. Into a 3-neck round bottomed flask was chai]ged 2.0 g (17 mmol) h amethylenediamine, 15 mL triethyl amine (109 mmol), 0.262 g (1.7 mmol) biphenyl as G.C. internal standard and 100 mL acetonitrile. The three-neck flask was fitted with an overhead stirrer, a CO2 gas inlet, a thermocouple and a diyice condenser. Into the diyice condenser was added a diyice/nf-xylene slush bath (-48°C). Carbon dioxide was added subsurface to the reaction mixture at room temperature giving rise to a heterogeneous solution. Over 90 min. the reaction mixture was cooled to 0°C and then to -20 C (o-xylene/dryice bath). Once equilibration was established at -20°C o-sulfobenzoic acid anhydride (12.5 g, 68 mmol) was added as a solid slowly over a 30 min period. Aliquots were taken periodically and were quenched by the addition of toluene/aq. HCl followed by analysis by G.C. (78%). 

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