Methanesulfonyl Chloride Research Articles

Synthesis of fluorine analogs of protoporphyrin potentially useful for diagnosis and therapy of cancer. IV. Synthesis of (trifluorovinyl)vinyl- and (1-chloro-2,2-difluorovinyl)vinyldeuteroporphyrins.

Trifluoro or chlorodifluoro analogs of protoporphyrin, the compounds in the title, were synthesized for use in the diagnosis and therapy of cancer. 3- Or 8-acetyldeuteroporphyrin dimethyl esters (2 and 3) were iodinated with iodine in the presence of potassium carbonate to the corresponding iodo compounds (5 and 6). The iodo compounds (5 and 6) were treated with bis(trifluorovinyl)zinc in the presence of tetrakis(triphenylphosphine)-palladium to give trifluorovinyl derivatives (7 and 8) in good yields. Reduction of the acetyl group of 7 and 8 with sodium borohydride afforded the corresponding hydroxyethyl derivatives (9 and 10). Compounds (9 and 10) were dehydrated with methanesulfonyl chloride and triethylamine to give (trifluorovinyl)vinyldeuteroporphyrin dimethyl esters (11 and 12). Treatment of 5 and 6 with bis(1-chloro-2,2-difluorovinyl)zinc in the presence of tetrakis(triphenylphosphine)palladium, followed by similar reactions as above gave (1-chloro-2,2-difluorovinyl)-vinyldeuteroporphyrin dimethyl esters (17 and 18).

New metal-binding ethyldiamino- and dicarboxy-products from Aspergillus niger industrial wastes.

The metal-binding ability of Aspergillus niger mycelial waste was improved by chemical modification. The latter was performed by introducing additional carboxy groups using oxidation methods or the introduction of the ethyldiamino group first by chlorination of A. niger using mesyl chloride and subsequent reaction of the product with ethylene diamine. Metal binding abilities of the products for Cd2+, Co2+, Ni2+ and Zn2+ were determined according to the Langmuir model, whereby pKD*-values of 3.88 up to 5.02 were revealed. Maximum capacities for the metals were found to be in the range 172 to 1064 mmol/kg.

ChemInform Abstract: New Aspect of Methanesulfonyl Chloride: Unusual Deoxygenations of Pyridine N‐Oxides with Methanesulfonyl Chloride and Triethylamine.

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New Aspect of Methanesulfonyl Chloride: Unusual Deoxygenations of Pyridine N-Oxides with methanesulfonyl Chloride and Triethylamine

Abstract Treatment of several pyridine N-oxides with an excess of methanesulfonyl chloride and triethylamine brought about a deoxygenation reaction to give efficiently the corresponding reduction products without chlorination of the pyridine nucleus.

Facile formation of chiral bicyclo[3.3.1]nonenes via regioselective cyclopropane cleavage of 1-methyltricyclo[4.3.0.0 2,9]nonan-8-ols

Generation of bicyclo[3.3.1]non-2-enes via a facile, regioselective homo-1,4-elimination reaction of either exo or endo 1-methyltricyclo[4.3.0.0 2,9]nonan-8-ols on treatment with pyridine and methanesulfonyl chloride, is described.

A new route to cumulenes by stannylation-deoxystannylation of propargylic alcohols. Application to synthesis of conjugated enyne[3]cumulene as a model compound of neocarzinostatin chromophore

Sequential treatment of a propargylic alcohol by BuLi and Bu 3SnCl gave a mixture of stannylated propargylic alcohol and stannylated allenyl alcohol, both of which were converted to a single [3]cumulene by deoxystannylation of the stannyl alcohols by treatment with methanesulfonyl chloride and triethylamine. The efficiency of the deoxystannylation has been compared with that of an analogous silyl counterpart and proved to be much more efficient. The method has been applied to synthesis of conjugated enyne[3]cumulene 3 as a model compound of neocarzinostatin chromophore.

Thermodynamics of methanesulfonic acid, methanesulfonyl chloride, and methyl methanesulfonate

The heat of formation of liquid methanesulfonic acid, -178.09 ± 1.48, was determined by measuring the heat of reaction of methyl thiolacetate with aqueous hypochlorite solution to give aqueous methanesulfonate and acetate. The heats of formation of liquid methanesulfonyl chloride, -126.91 ± 1.54, and methyl methanesulfonate, -164.34 ± 1.58, were determined by measuring the heats of reaction of methanesulfonyl chloride with water or methanol in the presence of a suitable basic catalyst. Heats of vaporization (based on vapor-pressure data), entropies (based on ab initio molecular orbital calculations), and free energies of transfer from gas phase to aqueous solution were calculated leading to values for the free energies of formation in aqueous solution. The free energies of formation so determined were methanesulfonic acid, -151.72 ± 2.68, methanesulfonyl chloride, -101.29 ± 1.96, and methyl methanesulfonate, -127.28 ± 2.08. From these values the free energies of hydrolysis (leading to unionized methanesulfonic acid) are methanesulfonyl chloride, -25.11 ± 3.04, and methyl methanesulfonate, -9.90 ± 2.48.Key words: sulfonic acids, heat of formation, free energy of formation, hydrolysis.

Methyleniminium salts as acylating agent — one step synthesis of baccatin III from 10-deacetylbaccatin III with high selectivity

New methyleniminium salts were investigated as acylating agent of 10-deacetylbaccatin III. Thus, synthesis of baccatin III was performed in one step with 79% isolated yield and 98% selectivity using the iminium salt prepared from mesyl chloride and N-ethylacetamide.

Synthesis of 6beta-[(2'-Aminoethyl)carboxamidomethyl]estradiol and preparation of estradiol probes.

Reformatsky reaction of 3, 17beta-bis[(2-trimethylsilyl)ethoxymethyl]-1,3, 5(10)-estratrien-6-one (2) with bromoethyl acetate and zinc gave the ester (3) in 60% yield which upon treatment with methanesulfonyl chloride in pyridine afforded the olefinic esters (4 and 5) as an endo and exo mixture (67:33 ratio) in 81% yield. Hydrolysis of the SEM protective groups in compounds 4 and 5 followed by hydrogenation of the resulting hydroxy compounds 6 and 7 using 10% Pd/C afforded an epimeric mixture (beta:alpha = 79:21) of 6-[(ethoxycarbonyl)methyl]estradiol (8a and 8b) in 95% yield. Hydrolysis of the ethyl esters (8a and 8b) using sodium hydroxide gave the acid (9a and 9b) in 81% yield. The epimeric mixture of acids (9a and 9b) was activated, treated with tert-butyl-N-(2-aminoethyl)carbamate (10), and purified by HPLC to afford 6beta-[[[(2-tert-butoxycarbonyl)amino]ethyl]carboxamidomethyl] estradiol (11) in 39% yield as the major isomer. Hydrolysis of the BOC group in compound 11 using TFA afforded the desired 6beta-[(2-aminoethyl)carboxamidomethyl]estradiol 12 in 50% yield. The biotinylated estradiol probe 14, fluorescent probe 16, and chemiluminescent probe 18 were prepared from 6beta-[(2'-aminoethyl)carboxamidomethyl]estradiol (12) and the corresponding biotin, 5-carboxyfluorescein, and 10-(3-sulfopropyl)-N-tosyl-N-(3-carboxypropyl)acridinium-9-carboxamide N-succinimidyl esters (13, 15, and 17) in 65-74% yield and 99% purity.

A convenient synthesis of fluoroalkyl ketones and sulfones from perfluoroisopropyl iodide

In the presence of hexaethylphosphorus triamide (HEPT), perfluoroisopropyl iodide is reacted directly with perfluoroalkyl acid halides, trifluoromethanesulfonyl fluoride, and methanesulfonyl chloride in benzonitrile to give the corresponding fluorinated ketones and sulfones. Diglyme is the solvent of choice for the reaction of pentafluorobenzoyl chloride with perfluoroisopropyl iodide in the presence of HEPT.

Preparation of alkenyl Fischer carbene complexes via aldol condensation with enolizable aldehydes

A method for the preparation of alkenyl chromium carbene complexes is described by an aldol condensation of enolizable aldehydes. The aldol condensation of pentacarbonyl methy(methoxy)methylene chromium is best performed with an aliphatic aldehyde that is precomplexed with tin tetrachloride and the elimination step is optimal with mesyl chloride and triethylamine.

Approaches to the D-E ring of the polyether antibiotic salinomycin using sharpless asymmetric dihydroxylation

The work described herein provides a model system for appendage of the E ring of epi-17-deoxy-( O-8)-salinomycin 3 onto bis-spiroacetal aldehyde 6. The conversion of aldehyde 7 to bicyclic ether 8 via silver assisted ring expansion of the mesylate derived from tetrahydrofuran alcohol 33 is described. Attempts to provide a stereoselective synthesis of epoxide 27 required for the preparation of 33 and hence 8 are reported. Alcohol 9 was prepared by chelation controlled addition of the Grignard reagent derived from bromide 15 to aldehyde 7. Bromide 15 in turn was prepared as a 9:1 E: Z mixture of isomers with the required E-stereochemistry being introduced via a stereoselective Julia ring opening of cyclopropane 20. Sharpless asymmetric dihydroxylation of alkenes 10 and 11 readily provided diols 22 and 25 [or 23 and 26 respectively], however, their subsequent conversion to epoxides 27 and 30 with retention of stereochemistry proved unsuccessful. Cyclic sulfites 37, 39 and sulfates 42, 45 were investigated as epoxide equivalents. Base induced cyclization of sulfites 37, 39 only afforded triols 21, 24. Analogous reaction using sulfates 42, 45 favoured endo cyclization to a tetrahydropyran ring, however, the acidic conditions required for hydrolysis of the initial alkyl sulfate effected undesired elimination of the resultant tertiary alcohol. Whilst a stereoselective synthesis of the correct epoxide 27 required for preparation of tetrahydropyran 8 via ring expansion of tetrahydrofuran 33 has not been achieved, these latter conversions have been successfully demonstrated by the conversion of epoxides 28 and 31 to a 1:1 mixture of tetrahydrofurans 33 and 34 which were separable by flash chromatography. Subsequent ring expansion of these tetrahydrofurans 33 and 34 to tetrahydropyrans 8 and 14 was effected upon treatment with methanesulfonyl chloride followed by silver carbonate.

Thermodynamics of methanesulfonic acid, methanesulfonyl chloride, and methyl methanesulfonate

Thermodynamics of methanesulfonic acid, methanesulfonyl chloride, and methyl methanesulfonate

N-(Cyanothioformyl)indoline; a new indoline ring forming reaction

Conversion of 2-hydroxymethyl- and 2-hydroxyethylaniline with Appel salt 1 into the arylimines 3 and 4 is accompanied by formation of the chloromethyl and chloroethyl derivatives 8 and 9. Triphenylphosphine converts compound 8 into the benzothiazine 6 but the chloroethyl compound 9 gives N-(cyanothioformyl)indoline 10 (55%) rather than the analogous benzothiazepine 12. Indoline 10 is also formed from 9 with sodium hydride (45%), and from the hydroxyethyl compound 4 with mesyl chloride and triethylamine (65%) or with excess of Appel salt 1 (38%). 1H and 13C NMR spectra show that the indoline exists in solution as two rotamers 10a and 10b. Indoline 10 is converted into the known cyanoformylindoline 13 by the nitrile oxide method, and is prepared independently from indoline and 4-chloro-5H-1,2,3-dithiazole-5-thione. Mechanisms are proposed for the new reactions.

A Convenient Synthesis of 3,3-Dichloroazetidines, a New Class of Azetidines.

A short synthesis of appropriately substituted 3,3-dichloroazetidines, a virtually unknown class of azetidines, is described. The reaction of 3,3-dichloro-1-azaallylic carbanions, generated from N-(1-aryl-2,2-dichloroethylidene)amines, with aromatic aldehydes produced alpha,alpha-dichloro-beta-hydroxy imines that, upon treatment with mesyl chloride, were converted into the corresponding beta-(mesyloxy) imines. Reaction of these alpha,alpha-dichloro-beta-(mesyloxy) ketimines with potassium cyanide or sodium borohydride in methanol furnished a variety of 2-cyano- and 2-methoxy-3,3-dichloroazetidines in a stereoselective manner. Reduction of beta-(mesyloxy) imines with sodium cyanoborohydride followed by cyclization with potassium carbonate in DMSO yielded 3,3-dichloroazetidines as well.

Synthesis of 4-Alkyl- or 4-Phenyl-7-methyl-1,2-dihydro-7H-imidazo[1,2,3-cd]purine-6,8-diones

New 4-alkyl- or 4-phenyl-7-methyl-1,2-dihydro-7H-imidazo[1,2,3-cd]purine-6,8-diones 1 were obtained by intramolecular alkylation of 8-alkyl- or 8-phenyl-9-(2-mesyloxyethyl)-1-methyl-9H-purine-2,6(1H,3H)-diones 5. The necessary compounds 5 were prepared from 6-[(2-hydroxyethyl)- amino]-3-methyl-5-nitrosopyrimidine-2,4(1H,3H)-dione (2), which was hydrogenated to 5-amino-6-[(2-hydroxyethyl)amino]-3-methyl derivative 3; consecutive reactions of the latter with an orthocarboxylate and mesyl chloride afforded 8-alkyl- or 8-phenyl-9-(2-hydroxyethyl)-1-methyl-9H-purine- 2,6(1H,3H)-diones 4 and compounds 5, respectively.

Facile synthesis of 2Z-2-Chloromethyl aryl-2-enoates

Abstract Triethylamine - Methanesulfonyl chloride has been employed as reagent for stereoselective synthesis of 2Z-2-(Chloromethyl)aryl-2-enoates from Baylis Hillman products in good yields at room temperature.

Synthesis of 17 beta-hydroxy esters of 4-estren-17 beta-ol-3-one and carbenicillin, ticarcillin, or functionalized oxacillin: potentially useful conjugates for beta-lactamase-based homogeneous immunoassays.

On the basis of the large range of kinetic constants of their substrates, beta-lactamases seem to be interesting enzymes for the development of homogeneous immunoassays. For this purpose, hapten-penicillin or -cephalosporin conjugates have to be prepared. The aim of this work is to couple the anabolizing steroid nandrolone to several penicillins characterized by extremely low K(m) and kcat values: ticarcillin, carbenicillin, and oxacillin. The easy decarboxylation of derivatives of phenylmalonic acid (carbenicillin) and thienylmalonic acid (ticarcillin) imposes the choice of very mild procedures which have been specifically adapted to each substance investigated. 4-Estren-17 beta-ol-3-one hemiphenylmalonate is conjugated to 6-aminopenicillanic acid after 1,1'-carbonyldiimidazole activation, while 4-estren-17 beta-ol-3-one hemi(3-thiophene)malonate is coupled to 6-aminopenicillanic acid after activation using methanesulfonyl chloride. Before conjugation of oxacillin, a carboxylated analogue of its side chain has been prepared. A procedure resorting to tert-butyl ester protection of the carboxyl group present on the isoxazole ring allows the binding of nandrolone to the remaining carboxyl followed, after specific deprotection, by the conjugation to 6-aminopenicillanic acid giving the oxacillin derivative. In this way, conjugates retaining immunological properties of nandrolone and high inhibiting power of beta-lactamases should be obtained.

Synthesis, 1H‐ and 13C‐NMR spectra, crystal structure and ring openings of 1‐methyl‐6,9‐epoxy‐9‐aryl‐5,6,9,10‐tetrahydro‐1H‐imidazo [3,2‐e] [2H‐1,5] oxazocinium methanesulfonate

AbstractThe methanesulfonic acid catalyzed reaction of 1‐(4‐chloro‐ and 2,4‐dichlorophenyl)‐2‐(1‐methyl‐2‐imida‐zolyl)ethanones 1a and 1b with glycerol produced cis‐ and trans‐{2‐haloaryl‐2‐[(1‐methyl‐2‐imidazolyl)methyl]‐4‐hydroxymethyl}‐1,3‐dioxolanes 2a and 2b with a 2:1 cis/trans ratio. Besides these five‐membered ketals, the reaction of 1a with glycerol afforded a small amount of trans‐{2‐(4‐chlorophenyl)‐2‐[(1‐methyl‐2‐imidazolyl)methyl]‐5‐hydroxy}‐1,3‐dioxane (3a, 7%). The reaction of methanesulfonyl chloride with cis‐1 formed the corresponding methanesulfonates, cis‐4, which rapidly cyclized to the title compounds 5. Base‐catalyzed ring opening of 5 furnished 1‐methyl‐5,6‐dihydro‐6‐hydroxymethyl‐8‐(4‐chloro‐ and 2,4‐dichlorophenyl)‐1H‐imidazo[3,2‐d][1,4]oxazepinium methanesulfonates 7. Acid‐catalyzed hydrolyses of 5 or 7 provided 1‐methyl‐2‐[(4‐chloro‐ and 2,4‐dichloro)phenacyl]‐3‐[(2,3‐dihydroxy)‐1‐propyl]imidazolium salts 12. Structure proofs were based on extensive 1H and 13C chemical shifts and coupling constants and structures of 3a and 5a were confirmed by single crystal X‐ray crystallography.

Facile preparation of chloromethylaryl solid supports using methanesulfonyl chloride and Hunig's base

Several commercially available hydroxymethylaryl resins were converted to their corresponding chloromethyl analogs by simple treatment with methanesulfonyl chloride and Hunig's base in DMF at 25 °C over 3 days. This mild method gave quantitative conversions as determined by elemental analysis and 13C NMR.