Compounds camphorsulfonic acid

A -sulfinyl chiral auxiliaries have been used to prepare enantiopure tetrahydro-P-carbolines and tetrahydroisoquinolines in good yields under mild reaction conditions. Both enantiomers of V-p-toluenesulfinyltryptamine 46 could be readily prepared from the commercially available Andersen reagents.Compound 46 reacted with various aliphatic aldehydes in the presence of camphorsulfonic acid at -78 °C to give the A-sulfinyl tetrahydro-P-carbolines 47 in good yields. The major diastereomers were obtained after a single crystallization. Removal of the sulfinyl auxiliaries under mildly acidic conditions produced the tetrahydro-P-carbolines 48 as single enantiomers. 

The synthesis of the right-wing sector, compound 4, commences with the prochiral diol 26 (see Scheme 4). The latter substance is known and can be conveniently prepared in two steps from diethyl malonate via C-allylation, followed by reduction of the two ethoxy-carbonyl functions. Exposure of 26 to benzaldehyde and a catalytic amount of camphorsulfonic acid (CSA) under dehydrating conditions accomplishes the simultaneous protection of both hydroxyl groups in the form of a benzylidene acetal (see intermediate 32, Scheme 4). Interestingly, when benzylidene acetal 32 is treated with lithium aluminum hydride and aluminum trichloride (1 4) in ether at 25 °C, a Lewis acid induced reduction takes place to give... 

L4165> have been used for this cyclization often catalyzed by TsOH or camphorsulfonic acid (CSA). Compound 358, used as an intermediate in the total synthesis of (—)-kaitocephalin, was prepared from 357 following this procedure shown in Equation (62) <20050L4165>. 

The chirality of compound 16b was completely inverted, to give 2,3-0-cyclohexylidene-L-ribonolactone (19), by means of a procedure (28) that involves oxidation of the hydroxymethyl group of 16b by ruthenium te-traoxide, followed by reduction of the lactone group. The resulting intermediate 1,5-lactone (18) underwent isomerization (with cyclohexylidene migration) upon refluxing in xylene, in the presence of a catalytic amount of D-camphorsulfonic acid [in Ref. (28) the formulas for the series were erroneously depicted]. 

D,L-10-Camphorsulfonic acid is used for the preparation of the corresponding chloride (p. 14). The optically active acid has been used widely for the resolution of basic compounds into optical antipodes. 

Compound 264 is unexpectedly stable against light, but can easily be oxidized to the sulfoxide 265 and the sulfone 266. Sulfoxide 265 can be isolated and a-activated by reaction with acetic anhydride (Scheme 4.46). a-Acetoxylated tetrahydrothio-phene 267 has 0,S-acetal-like reactivity and can be functionalized with various alcohols or thiols under acid catalysis with camphorsulfonic acid (CSA) (268). 

The retrosynthesis of this compound by Batey and co-workers [96] recognized that the unprecedented hexahydropyrrolo[3,2-c]quinoline core could be synthesized using a three-component Pavarov hetero-Diels-Alder reaction [97]. For this synthetic strategy to be successful, however, reaction conditions that favor the exo approach of the dienophile over the endo approach had to be found. For this purpose, a variety of protic acids were tested, and it was found that the reaction was best carried out in the presence of camphorsulfonic acid (CSA). Indeed, a mixture of 4-aminobenzoate 200 and N-Cbz 2-pyrroline 201 were stirred at room temperature in the presence of catalytic CSA to afford exo cyclo-adduct 203 as the major product (Scheme 12.28). The N-Cbz 2-pyrroline served as both an aldehyde equivalent and a dienophile in this context. The Diels-Alder adduct 203 already bore all the requisite functionalities for the successful completion of the synthesis, which was achieved in six additional steps. 

Hydrolysis of ( )-colchicine with 0.1 N HC1 affords ( )-colchiceine, and ( )-deacetylcolchiceine is obtained on hydrolysis of ( )-colchicine with 20% H2SO4 and AcOH. Treatment of ( )-deacetylcolchiceine with trifluoroacetic anhydride afforded a trifluoroacetamide which, on methyl-ation with diazomethane, gave a mixture of ( )-trifluoroacetyldeacetyl-colchicine and ( )-trifluoroacetyldeacetylisocolchicine. The latter compounds were separated by chromatography and hydrolyzed with potassium carbonate in acetone/water to give ( )-deacetylcolchicine and ( )-deacetylisocolchicine (37). An easy chemical resolution of ( )-de-acetylcolchicine with 10-camphorsulfonic acid in methanol afforded the optically pure amines, and (+)- and (-)-colchicine after N-acetylation. 

The enol acetate 77 of 3,4-dihydro-7-methoxy-5-methyl-l-(2l/)-naphthalenone was converted to the acid 78 by ozonolysis and hydrolysis and this by a Wittig reaction with a-methoxyethyltriphenyl-phosphonium chloride gave 79. Compound 79 was converted into 80 by a series of reactions, five in number, which in turn was converted into 81 by reaction with potassium in -butanol. The methyl ester of compound 81, one isomer of which was recognized as that having the correct stereo structure, was converted to 82 by heating with acetic anhydride and 10-camphorsulfonic acid. Subsequent steps involved ozonization, reaction with V,iV -carbonyldiimidazole, lactam formation, reaction with pyridinium bromide perbromide, reaction with sodium hydride, and a further series in which (+ )-oxodendrobine (83) was ultimately obtained. Reduction of the latter to ( )-dendrobine... 

The formation of 0,0-acetals from carbonyl compounds and alcohols takes place according to the mechanism of Figure 9.12. As acidic catalysts one uses a mineral acid (HC1 or H2S04) or a sulfonic acid (p-toluenesulfonic acid, camphorsulfonic acid, or a strongly acidic cation exchange resin) ... 

Illustrated in Table III are the solvent effects. The carbonyl compound used is a-phenylpropionaldehyde and the optically active acid is D-camphorsulfonic acid. The figure reveals that when hydrolysis is carried out, less miscible solvents are more effective suggesting that interfacial reactions are effective for stereoselectivity of asymmetric transformations. 

Dioxene can be used to prepare trisubstituted annulated furans in a three-step sequence. By lithiation of 1,4-dioxene, followed by carbonyl addition, an allylic alcohol 13 is obtained, which can be reacted with silyl enol ethers in the presence of a Lewis acid to furnish disubstituted dioxanes of type 14. These compounds rearrange to furans under mild conditions upon treatment with camphorsulfonic acid (Scheme 16) <1999TL2521>. 

Chemical Resolution of Compounds Containing Basic Groups. 3-Bromocamphor-8-sulfonic acid has been widely used as a resolving agent for compounds containing basic groups. A number of primary (1), secondary (2), and tertiary (3) amines as well as oxazolines (4) have been resolved by the formation of diastereomeric salts derived from 3-bromo-8-camphorsulfonic acid. 

Preparative Methods methyl phenyl sulfoxide is treated with Hydrazoic Acid (generated by addition of sulfuric acid to a slurry of sodium azide) in chloroform maintained at 45 °C to produce -methyl- -phenylsulfoximine. The latter can be readily resolved using 10-Camphorsulfonic Acid, from the (+)-acid the salt of (+)-(5)-5 -methyl-5 -phenylsulfoximine is obtained pure by recrystallization. The Clarke-Eschweiler procedure using Formaldehyde and Formic Acid provides an effective method for conversion of the N-H sulfoximine to the title compound. ... 

Resolving Agent for Certain lypes of Amines. TAPA has also been used as resolving agent for some amines that formed either unstable, insoluble, or noncrystalline salts with common resolving acids. Compounds (3) and (4) were among those resolved with TAPA, whereas camphor-10-sulfonic acid, 3-bromo-8-camphorsulfonic acid, 0,0-di-p-toluoyl-(+)-tartaric acid, (+)-tartaric acid, and (+)-camphoric acid could not be used. ... 

The submitters purchased d-menthol from TCI and the checkers obtained this compound (99%, 98% ee) from Aldrich Chemical Company, Inc. Menthol was used as received. D-(-i-)-camphorsulfonic acid (99%) was purchased from Avocado and used as received. Benzene was purchased from EM Science and used as received. 

Xanthate 446 undergoes cyclization in the presence of camphorsulfonic acid via a radical chain reaction initiated by a small amount of lauroyl peroxide to give pyrroloimidazoles 449 in 56% yield. The use of an acid and anhydrous medium inhibits nucleophilic attack of the basic heterocycles at the xanthate moiety and allows radical reactions to occur. Fused heteroaromatic compounds can also be prepared directly from benzimidazole carrying an N-alkenyl substituent and xanthates by a tandem radical addition/cyclization to provide, for example, pyrrolobenzimidazole 453 in 57% yield (Scheme 106) <2002OL4345>. 

Effective catalysts for preparing the polyformals were p-toluenesulfonic acid, camphorsulfonic acid, methanedisulfonic acid, and perchloric acid. Various other acidic compounds were evaluated as catalysts with tetramethylcyclobutanediol. In these experiments, 0.5 to 1.0 gram of acidic compound per mole of tetramethylcyclobutanediol was normally added. If insufficient water was obtained, more catalyst was added. If the prepolymer was obtained but an appreciable amount of brown color was present, less catalyst was then used. Compounds which did not catalyze the reaction (no water obtained) were phosphoric acid, zinc chloride, trifluoroacetic acid, and heptafluorobutyric acid. Incomplete reactions (insufficient water) took place with concentrated hydrochloric acid, concentrated nitric acid, zinc fluoroborate, or Amberlite IRC-50 ion exchange resin as catalyst. A prepolymer was obtained when boron trifluoride etherate was used, but buildup did not take place in the solid phase (catalyst probably too volatile). Brown or speckled-brown polymers (after solid-phase buildup) were obtained with catalysts containing sulfonic acid groups (benzenesulfonic, dodecylbenzenesulfonic, sulfo-acetic, methanetrisulfonic, sulfuric, p-toluenesulfonic, camphorsulfonic, and methanedisulfonic acids). To obtain white polymers from tetramethylcyclobutanediol it was necessary to treat the solvent and prepolymer reaction mixture as previously described. (White polyformals were obtained from the other diols without this treatment.)... 

Treatment of 2,3,6,7-tetramethoxy-9-chloromethylphenanthrene with pyrryl magnesium bromide yielded 2-(2,3,6,7-tetramethoxy-9-phenanthrylmethyl)pyrrole (XI) which was reduced to the corresponding pyrrolidine. The A -formyl derivative of the latter underwent smooth cyclization with phosphorus oxychloride to the quaternary salt (XII) reduced in good yield to ( + )-tylophorine by sodium borohydride. The synthetic compound was resolved through (-f- )-camphorsulfonic acid into ( — )-tylophorine (mp 292° [aJu — 11.5°), and (- - )-tylophorine (mp 292° [a]p -f-12.16°). 

Diltiazem hydrochloride and its related compounds can be separated in both bulk drug and finished tablets using a Waters pBondapak C18 column (10 pm particle size, 300 mm x 3.9 mm I.D.) and a mobile phase of buffer methanol acetonitrile (50 25 25, v/v) at a flow rate of about 1.6 mL/minute. The buffer is 0.1 M aqueous sodium acetate containing 5mM d-camphorsulfonic acid (99%) adjusted to pH 6.2 with 0.1 M aqueous sodium hydroxide. Detection of the compounds is achieved using UV absorbance at 240 nm. The method provides for the resolution of trans-diltiazem and seven known and unidentified related compounds. Diltiazem hydrochloride elutes at approximately 21 minutes under these conditions. The minimum detectable amounts are less than 0.1% for all related compounds except for one of the synthetic intermediates for which there is a limit of about 2% (27). 

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