Saccharin preparation

Sugars. Ordinary honey contains up to 8% of saccharose, but some varieties (from conifers) may contain 11%. Proportions larger than 8% in the one case, or than 11% in the other, usually denote addition of sugar it should, however, be borne in mind that bees fed with sugar or saccharine preparations may give honey with larger proportions of saccharose than those in cheated. 

Although benzenesulphonyl chloride has for simplicity been used in the above discussion, tolucne-/>- sulphonyl chloride, CHaCeH SO Cl, is more frequently used in the laboratory, owing to its much lower cost, the latter being due in turn to the fact that toluene-p-sulphonyl chloride is a by-product in the commercial preparation of saccharin. Toluene-p sulphonyl chloride is a crystalline substance, of m.p. 68° the finely powdered chloride will, however, usually react readily with amines in the Schotten-Baumann reaction it does not react so readily with alcohols, but the reaction may be promoted considerably by first dissolving the chloride in some inert water-soluble solvent such as acetone. 

Pseudo saccharin chloride (II) is prepared by the action of phosphorus penta-chloride upon saccharin (I) ... 

Benzisothiazole 1,1-dioxides and saccharin derivatives are best prepared by cyclization of o-substituted benzenesulfonamides (see Section 4.17.9.1.2). 

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>. 

Bode and co-workers have extended the synthetic ntility of homoenolates to the formation of enantiomerically enriched IV-protected y-butyrolactams 169 from saccharin-derived cyclic sulfonylimines 167. While racemic products have been prepared from a range of P-alkyl and P-aryl substitnted enals and substitnted imi-nes, only a single example of an asymmetric variant has been shown, affording the lactam prodnct 169 with good levels of enantioselectivity and diastereoselectivity (Scheme 12.36) [71], As noted in the racemic series (see Section 12.2.2), two mechanisms have been proposed for this type of transformation, either by addition of a homoenolate to the imine or via an ene-type mechanism. 

Both solid and liquid dosage forms may contain saccharin. Saccharin is a nonnutritive sweetening agent, which is 300 times as sweet as sucrose. In a survey of sweetener content of pediatric medications, seven out of nine chewable tablets contained saccharin (0.45-8.0 mg/tablet) and sucrose or mannitol. Seventy-four of the 150 liquid preparations investigated contained saccharin (1.25-33 mg/5 mL) [62], Saccharin is a sulfanamide derivative that should be avoided in children with sulfa allergies [54],... 

It is recommended that daily saccharin intake be maintained below 1 g because of a risk of bladder cancer. A lifetime daily diet containing 5-7.5% saccharin has induced bladder tumors in rats [69]. However, it is probable that saccharin is only a very weak carcinogen in humans. The amount contained in pharmaceutical preparations is well below the recommended maximum human daily intake. 

Chiral A-substitutcd benzisothiazole-3-one-1,1-dioxide (saccharin) derivatives 258 are synthesized via the direct ortho-lithiation of 3-A-arylsulfonyloxazolidine-2-ones 257 using LDA and HMPA <06TL6405>. Compounds 257 are readily prepared from (X)-amino acids. 

Various saccharin derivatives 260 have been prepared by chromium (VI) oxide catalyzed H5IO6 oxidation of substituted ort/ro-toluenesulfonamides 259 <06T7902>. The reaction presumably proceeds through a benzylic radical intermediate 261 generated from the... 

Determination of saccharin in table top preparations -Spectrometric method... 

Two main standards were developed, one for the sweeteners showing UV absorption, i.e. acesulfame, aspartame and saccharin,36 and a separate standard for cyclamate37 which does not show a substantial UV absorption. Both standards use HPLC and propose specific sample preparation procedures. HPLC is also the suitable technique for the quantitative determination of sucralose.38... 

The sweetening agent saccharin is also derived from a sulphonamide it is prepared from toluene-o-sulphonamide by oxidising the CHs-group to carboxyl with permanganate ring closure is subsequently brought about by the action of concentrated hydrochloric acid ... 

The best preparative method of obtaining terephthalic acid is to oxidise the sodium salt of p-toluic acid with permanganate at the temperature of the water bath. In the same way toluene can be converted into benzoic acid, and an important technical example of this reaction is the oxidation, of o-tolylsulphonamide to saccharin. 

V-Acylsaccharins prepared by treatment of the sodium salt of saccharin with acyl chlorides were reduced by 0.5 molar amounts of sodium bis(2-methoxyethoxy)aluminum hydride in benzene at 0-5° to give 63-80% yields of aliphatic, aromatic and unsaturated aldehydes [1108 Fair yields (45-58%) of some aliphatic aldehydes were obtained by electrolytic reduction of tertiary and even secondary amides in undivided cells fitted with platinum electrodes and filled with solutions of lithium chloride in methylamine. However, many secondary and especially primary amides gave 51-97% yields of alcohols under the same conditions [130]. 

The standard means for preparing oxicams 285, initially developed by Lombardino, is through the base-promoted rearrangement reaction of isothiazole dioxides 286, which in turn are prepared from saccharin derivatives such as 287 (Scheme 40) <1981AHC(28)73>. The oxicam core can be further derivatized by N-alkylation of oxicam 285 and amidation of the C-3 ester functionality of 288 to form the common drug scaffold 289. 

Zajic has described an extremely convenient and high yielding preparation of Al-bromo-saccharin, which is an excellent source of electrophilic bromine, by treatment of saccharin with KBrOs and sulfuric acid in aqueous acetic acid <99SC1779>. 

The use of chiral A-acylated sultams 1 as auxiliaries for diastereoselective alkylation and related reactions has emerged as a useful and versatile method for the construction of chiral compounds. Both enantiomers of 10.10-dimethyl-4-a2a-3-thiatricyclo[S.2.1,0 -5]decane 3,3-dioxide (bomane-10,2-sultam) have been employed1-6 and are now commercially available. A chiral sultam prepared from saccharin has also been used for a variety of asymmetric transformations8,9. 

All of the 4-carbon saccharinic acids possible have been prepared and characterized.132 The 4-carbon metasaccharinic acid has been encountered frequently,1,133-137 and a racemic mixture of the 2-methyl-glyceric acids (2,3-dihydroxy-2-methylpropanoic acids) was obtained from 4-O-methyl-D-threose.136... 

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