Saccharin Synthesis

Saccharin, 12 42, 15 587. See also Synthetic sweeteners Saccharin analogues, 24 236 Saccharin blends, 24 235 Saccharin production, newer process for, 24 235-236 Saccharin synthesis... 

Scheme 40 Industrial saccharin synthesis with chromic acid as mediator.

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]. 

S.4.2.4 Tracking Origin of Sulfur Atom in Saccharin Synthesis... 

Two new pyridone derivatives (14) and (15) have been prepared by cycloaddition of saccharin pseudochloride (16 R = Cl) with Danishefsky s diene and by treatment of (16 R = Me) with ciimamoyl chloride. The synthesis of two more ting expanded derivatives (17) and (18) via cycloaddition to benzisothiazoles was also described <96T3339>. 

Problem 16.61 Write structures for compounds (A) through (C) in the synthesis of saccharin. 

In addition to the synthesis of saccharin, also a number of other side-chain oxidations have been studied leading to aromatic carboxylic acids by indirect electrochemical oxidation using chromic acid as oxidizing agent. They include the oxidation of p-nitrotoluene 2,4-dinitrotoluene toluene, p-xylene, and p-tolualdehyde... 

Saccharin, 2-methyl-reduction, 6, 152 Saccharin, 6-nitro-reduction, 6, 154 Saccharin, thio-hydrolysis, 6, 161 methylation, 6, 160 Safranines applications, 3, 196 Safrole derivatives toxicity, 1, 139-140 occurrence, 6, 781 Safrole, 1-hydroxy-toxicity, 1, 140 Salazosulfapyridine intestinal disorders and, 2, 517 Salicylaldehydes chroman synthesis from, 3, 782 Salicylanilides ... 

Toluene-o-sulphonamide is an intermediate in the synthesis of saccharin (Expt 6.42). Upon oxidising toluene-o-sulphonamide with potassium permanganate in alkaline solution, the sodium salt of o-sulphonamidobenzoic acid is formed, which on acidification with concentrated hydrochloric acid passes spontaneously into the cyclic imide of o-sulphobenzoic acid or saccharin. Saccharin itself is sparingly soluble in cold water, but the imino hydrogen is acidic and the compound forms a water-soluble sodium salt. The latter is about 500 times as sweet as cane sugar. 

F. J. Lopez Aparicio, I. Izquierdo Cubero, and M. D. Portal Olea, Synthesis of saccharinic acid derivatives, Carbohydr. Res., 129 (1984) 99-109. 

S. Basavoju, D. Bostrom, S.P. Velaga, Indomethacin-saccharin cocrystal design, synthesis and preliminary pharmaceutical characterization, Pharm. Res. 25 (2008) 530-541. 

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