Showing papers on "Diazomethane published in 1990"

Pyrethroid metabolism: microsomal oxidase metabolites of (S)-bioallethrin and the six natural pyrethrins

Abstract: Metabolism of the chrysanthemates (S)-bioallethrin, cinerin I, jasmolin I, and pyrethrin I by NADPH-dependent oxidases of mouse liver microsomes yields 13-18 metabolites in each case oxidized at the methyl, methylene, and alkenyl substituents to form alcohols, aldehydes, carboxylic acids, epoxides, and dihydrodiols. Rat microsomes are more specific than mouse microsomes in hydroxylating the (E)-methyl substituent of the 2-methylpropenyl moiety compared with other molecular sites. Metabolites in the urine of allethrin-treated rats include compounds modified in both the 2-methylpropenyl and allyl moieties as free carboxylic acids and glucuronides. The pyrethrates cinerin II, jasmolin II, and pyrethrin II undergo microsomal hydrolysis of the methoxycarbonyl group and oxidation of the butenyl, pentenyl, and pentadienyl substituents to alcohols, epoxides, and dihydrodiols. Metabolites of these chrysanthemates and pyrethrates are tentatively identified by chemical ionization mass spectrometry following treatment with diazomethane or diazoethane and bis(trimethylsilyl)acetamide and separation by high-resolution gas chromatography with hydrogen as the carrier gas.

A Preparative Nitroxyl-radical Coated, Graphite Felt Electrode for the Oxidation of Alcohols

Abstract: The graphite felt electrode, coated with ca. 3 wt% polyacrylic acid, was modified by successive reactions with hexamethylenediamine (for cross-linking), 4-amino-2,2,6,6-tetramethylpiperydinyl-1-oxyl(4-amino-TEMPO) and diazomethane (for methylation). Properties of the electrode, were compared with a non-crosslinked and non-methylated one, a crosslinked and a non-methylated one, and a crosslinked and incompletely methylated one; the present electrode was stable and oxidized nerol to neral selectively with turnover number > 1560.

1,2,4-Diazaphosphole nucleosides. Synthesis, structure, and antitumor activity of nucleosides with a lambda 3 phosphorus atom.

Abstract: Glycosylation of 1,2,4 lambda 3-diazaphosphole (4) under Lewis acid catalyzed conditions gave 1-alpha-D-ribofuranosyl-1,2,4 lambda 3-diazaphosphole (5) as the only product. Ethyl 1,2,4 lambda 3-diazaphosphole-3-carboxylate (10) was synthesized by the cyclocondensation of ethyl (chlorophosphinidene)(trimethylsilyl)acetate (8) with (trimethylsilyl)diazomethane and subsequent desilylation with tetra-n-butylammonium fluoride. Reaction of 10 with methanolic ammonia at 80 degrees C gave 1,2,4 lambda 3-diazaphosphole-3-carboxamide. Glycosylation of 10 using trimethylsilyl triflate catalyst followed by ammonlysis gave the ribavirin (1) analogue 1-beta-D-ribofuranosyl-1,2,4 lambda 3-diazaphosphole-3-carboxamide (11). Acetylation of 11 and subsequent treatment with phosphorus pentasulfide gave 2',3',5'-tri-O-acetyl-1-beta-D-ribofuranosyl-1,2,4 lambda 3-diazaphosphole-3- thiocarboxamide (13). Deprotection with methanolic ammonia gave 1-beta-D-ribofuranosyl-1,2,4 lambda 3-diazaphosphole-3-thiocarboxamide (14). Compound 14 gave a 25% increase in life span (ILS) against L1210 in female BDF1 mice. The anomeric configuration and site of glycosylation of 5 and 13 were established by single-crystal X-ray crystallography.

Palladium(II)-Catalyzed Cyclopropanation of Simple Allyloxy and Allylamino Compounds and of 1-Oxy-1,3-butadienes with Diazomethane

Abstract: (Alkoxymethyl)-, (aminomethyl)-, (2-alkoxyethenyl)-, (2-acetoxy-ethenyl)-, and (2-siloxyethenyl)cyclopropanes are obtained in high yields by reaction of allyl alcohol or derivatives, alllylamines, 1-alkoxy-, 1-acetoxy-, and 1-trimethylsiloxy-1,3-butadienes with diazomethane in dichloromethane/diethyl ether in the presence of bis(benzonitrile)palladium dichloride

Mammalian Alkaloids: O‐Methylation of (±)‐Norcoclaurine‐1‐carboxylic Acid and Related Isoquinolines Including (S)‐ and (R)‐Norcoclaurine with 14C‐Labeled S‐Adenosyl‐L‐Methionine in Presence of Mammalian Catechol O‐Methyltransferase

Abstract: (±)-Norcoclaurine-1-carboxylic acid (5) and the derived dihydroisoquinolinone 6 (present as quinonemethide 6a at pH 7) afforded, on methylation with 14C-labeled S-adenosyl-L-methionine in the presence of mammalian catechol O-methyltransferase, exclusively the 7-O-methylated congeners 7 and 9, respectively. High stereoselectivity of the O-methylation was observed with (−)-(S)- and (+)-(R)-norcoclaurine (2a and 2b, resp.), affording 80% of 6-O-methylated isoquinoline 12 and 20% of the 7-O-methylated isomer 11 from 2a, and the reversed proportion of 12 and 11 from 2b. Synthesis of the reference amino acid 8 was achieved by Pictet-Spengler condensation of O-benzyl-protected dopamine 17 with benzyl-protected keto acid 20 ( 21) followed by methylation with diazomethane (22 + 23) and removal of the protecting groups by acid hydrolysis. It is considered unlikely that amino acids such as 5 constitute important precursors in the biosynthesis of isoquinolines related to reticuline.

An approach to trapping .gamma.-glutamyl radical intermediates proposed for vitamin K dependent carboxylase: .alpha.,.beta.-methyleneglutamic acid

Abstract: The vitamin K dependent carboxylase activates the glutamyl gamma-CH of substrate peptides for carboxylation by producing a gamma-glutamyl free radical, a gamma-glutamyl carbanion, or through a concerted carboxylation. We propose to intercept the putative gamma-glutamyl free radical by the intramolecular rearrangement of a substrate containing the alpha,beta-cyclopropane analogue of glutamic acid. The rearrangement of cyclopropylcarbinyl radicals into 2-butenyl radicals is rapid, exothermic, and considered diagnostic of free-radical formation. 1-Amino-2-(carboxymethyl)cyclopropane-1-carboxylate, the beta-cyclopropane analogue of glutamic acid, was synthesized starting from diethyl alpha-ketoglutarate. The alpha-keto ester was first treated with benzonitrile in sulfuric acid, to yield diethyl alpha,alpha-dibenzamidoglutarate. The alpha,alpha-dibenzamido acid was cleaved to produce the alpha,beta-dehydroamino acid and benzamide on treatment with p-toluenesulfonic acid in hot benzene. Diazomethane addition to the dehydroamino acid resulted in cycloaddition of diazomethane and production of the pyrazoline, which upon irradiation lost N2 to give the protected cyclopropane-containing amino acid analogue. Acidic hydrolysis of the N-benzoyl-alpha,beta-methyleneglutamate diethyl ester resulted in the production of the unprotected amino acid, alpha,beta-methyleneglutamic acid, in high yield. A single dehydroamino acid and a single methyleneglutamic acid isomer were produced in this synthesis; both are identified as the Z isomer, the former by NMR using the nuclear Overhauser effect and the latter through X-ray crystallographic analysis of N-benzoyl-alpha,beta-methyleneglutamate diethyl ester. Saponification of a N-protected methyleneglutamic acid dialkyl ester using limiting alkali was shown to selectively yield the alpha-alkyl ester gamma-acid. The reaction was used to produce alpha,beta-cyclopropane-containing analogues of the carboxylase substrates N-t-Boc-L-glutamic acid alpha-benzyl ester and N-benzoyl-L-glutamic acid alpha-ethyl ester. The cyclpropane-containing analogues were tested and found to be neither substrates for nor inhibitors of the rat liver microsomal vitamin K dependent carboxylase. The inability of the enzyme to recognize these substrate analogues is attributed to the alpha-alkyl substitution, which apparently abolishes substrate binding.

STEREOSPECIFIC FORMATION OF A 1,2λ3 -AZAPHOSPETANE IN THE THERMOLYSIS OF BIS[BIS(DIISOPROPYLAMINO)PHOSPHANYL] DIAZOMETHANE

Abstract: Heating of bis[bis(diisopropylamino)phosphanyl]diazomethane 7. in refluxing benzene for 48 hours, quantitatively led to the corresponding 1.2λ3-azaphosphetane 9 as only one diastereoisomer. This result is explained in terms of carbene insertion into a methin-CH bond of an isopropyl substituent. The regiospecificity and the stereospecificity of the ring closure is discussed. Treatment of 9 with elemental sulfur afforded the corresponding 1.2.2λ3-azathiophosphetane 10 which has been characterized b X ray crystallo raphy: C25H56N4P2S2, space group P2(l)/n, a = 13.628 (3) A, 6 = 19.369 (5) A, c 112.485 (4) A, V = 3073 (3) A3.

Gas chromatographic-mass spectrometric determination of six sulfonamide residues in egg and animal tissues.

Abstract: A gas chromatographic-mass spectrometric method using selected ion monitoring mode for simultaneous determination of 6 sulfonamides in egg and edible animal tissues has been developed Sulfonamides are extracted from a sample with acetonitrile The extract is passed through a silica cartridge column and concentrated Diazomethane in ether is added to methylate sulfonamides After evaporation, the residue is dissolved in methylene chloride and cleaned up by silica gel column chromatography The methylene chloride eluate containing sulfonamide-methyl derivatives is evaporated to dryness, redissolved in ether and partitioned between 6N hydrochloric acid The acid phase is made alkaline, extracted with ether, and the ether solution, after concentration, is analyzed by gas chromatography-mass spectrometry in selected ion monitoring mode Average recoveries from egg and silver salmon fortified at 1 and 02 ppm levels with 6 sulfonamides are 992 and 843%, respectively; coefficients of variation are 703 and 1120%, respectively Detection limits are 001-005 ppm

Methylierung 3,3′-dihydroxylierter 2,2′-Binaphthyl-1,4;1′,4′-dichinone / Methylation of 3,3′-Dihydroxylated 2,2′-Binaphtho-1,4;1′,4′-quinones

Abstract: Monomeric hydroxy-p-quinones (1) are in equilibrium with the corresponding o-quinones (2) and on methylation, a mixture of both isomeric ethers is obtained In contrast, dimeric hydroxynaphthoquinones with the 3 a-skeleton in treatment with diazomethane are yielding only p-quinone ethers of type 3b

Synthesis and Spectroscopic Properties of New Rose Bengal and Eosin Y Derivatives.

Abstract: Selective esterification of purified Rose Bengal and Eosin Y have been carried out by reaction with methyl iodide, benzyl chloride or p-isopropylbemyl chloride. The lactonic form of each dye reacts with diazomethane producing mixtures of the monomethyl ether and the dimethyl ether of the lactone, and the methyl ether of the methyl ester of the tautomeric quinonoid form. On heating, Rose Bengal decarboxylates in dimethylformamide solution, while Eosin Y loses a bromine atom in dimethylsulphoxide. The structures of all the products obtained have been studied by the usual Spectroscopic techniques. HPLC data are also reported.

Analysis of residues of phosphonate in plant material

Abstract: A rapid quantitative method for the determination of phosphonate is presented Phosphonate in the sample extract is reacted with diazomethane and then determined using gas chromatography Low detection limits and good recoveries for a wide range of samples have been achieved

Sulfur-Containing Polybromoindoles from the Red Alga Laurencia brongniartii.

Abstract: Six new polybromoindoles (9-14) have been isolated from the red alga Laurencia brongniartii. Two were optically active sulfoxides, the itomanindoles A (12) and B (13) and one was a bisindole (14). The structures of 12 and 14 were elucidated by X-ray analysis. The sulfoxides 12 and 13 were readily converted with diazomethane to the corresponding N-methyl derivatives. Treatment with acetic anhydride at room temperature gave the same indolenine (24) as the major product.

Umsetzungen von Meldrumsäure mit Isocyanaten und Isothiocyanaten

Abstract: Meldrum's acid (1) reacts with isothiocyanates and LiH as base, yielding after alkylation the ketene-S,N-acetales3,4 and5. Protonation of the lithium-thiolate2 gives the thioamides7 with tautomers8, which can be methylated with diazomethane to9. From1 and7 it is possible to obtain the amides12.2 reacts with α-bromo-carboxylic esters and bromo-acetone, yielding thiazolidones15,16 and thiazolines18.

Reactions of 1,2-oxaphospholene 2-oxides. 6. Free-radical and nucleophilic substitution at C5: anomalous proton-transfer behavior of cyclic ketals

Abstract: The free-radical bromination of 3,5-di-tert-butyl-2-hydroxy-1,2-oxaphosphol-3-ene 2-oxide (1b) with N-bromosuccinimide (NBS) gave the corresponding 5-bromo-3,5-di-tert-butyl-2-hydroxy-1,2-oxaphosphol-3-ene 2-oxide (3) in good yield. Bromide 3 underwent methanolysis to give 3,5-di-tert-butyl-2-hydroxy-5-methoxy-1,2-oxaphosphol-3-ene 2-oxide (7) or hydrolysis to 3,5-di-tert-butyl-2,5-dihydroxy-1,2-oxaphosphol-3-ene 2-oxide (8), both crystalline compounds. Treatment of 8 with diazomethane led to dimethyl (Z)-2,2,6,6-tetramethyl-3-oxohept-4-en-5-ylphosphonate (10), indicating that 8 is in equilibrium with its open phosphonic acid isomer

Total synthesis of analogues of the β-lactam antibiotics. Part 5. 3-Thiacepham-4-exo-carboxylates and their 1,1,3,3-tetraoxides

Abstract: t-Butyl hydroxy{4-[(Z)-2-(methoxycarbonyl)vinylthio]-2-oxoazetidin-1-yl}acetate (19a) was transformed into t-butyl 2-endo-methoxycarbonylmethyl-3-thiacepham-4-exo-carboxylate (20a) by sequential reactions involving thionyl chloride, potassium thioacetate, and cyclohexylamine. Oxidation of compound (20a) with potassium permanganate gave the 1,1,3,3-tetraoxide (23a), the structure of which was established by X-ray crystallography. The exceptional acidity of the 2- and 4-hydrogen atoms of compound (23a) was revealed by their replacement with deuterium atoms in the presence of deuterium oxide and with methyl groups in the presence of diazomethane. Cleavage of the t-butyl ester function of the thiacepham tetraoxide (23a) was effected by trifluoroacetic acid but the resultant acid (23b) underwent a rapid decarboxylation in water to give 2-endo-methoxycarbonylmethyl-3-thiacepham 1,1,3,3-tetraoxide (26a).

Reactions with 2-thiohydantoin derivatives: synthesis of mannich bases and imidazothiazole derivatives

Abstract: 5-Arylidene-2-thiohydantoins (la-c) and 5-arylazo-1-phenyl-2-thiohydantoins (7a, b) were condensed with formaldehyde and primary or secondary aromatic amines to give the corresponding Mannich bases (2a-f) and (8a, b) respectively, which could also be converted into the educts (la-c) and (7a, b) by boiling in ethanolic HCI. On treatment of (2a-f), (5a-c) and (8a, b) with an ethereal diazomethane the colourless cyclopropane products (3a-c) and yellow N-methyl substituted compounds (9, b) were isolated respectively. Alkylation of (2d-f) with methyl iodide and (la-e) with 3-chloropentane-2,4 dione gave the corresponding 2-alkylmercapto derivatives (5a-c) and (2a-c) respectively, the former of which on hydrolysis by boiling ethanolic HCI afforded the hydantoin derivatives (6a-c). Cyclization of (12a-c) using polyphosphoric acid resulted in the formation of imidazothiazole derivatives (13a-c). The structure of the isolated products were established by elemental analyses and spectral data studies.

Study of the reaction of diazomethane with dansylated amino acid derivatives by gas chromatography/mass spectrometry

Abstract: Since the methylation of acids with diazomethane is widely used in trace analysis, it is extremely important for those using this technique to be alert to the analysis of compounds containing other functional groups which might become methylated with high concentrations of diazomethane. We have shown that by adding an excess of diazomethane to dansylated amino acids, not only is the methyl ester formed, but the products can be further methylated. The only remaining acidic hydrogen in the molecule is the hydrogen attached to the sulfonamide nitrogen, and the mass spectrometry results indicate that the methyl ester is formed first, and the N-methylated derivative is formed with excess diazomethane.