Synthesis of Functionalised Cyclohexanes from Carbohydrates

<p>Beta-D-glucopyranose pentaacetate was photobrominated to give the 5-baromide from which 6-deoxy-Beta-D-xylo-hex-5-enopyranose tetraacetate was obtained by reductive elimination. This reaction sequence represents an efficient new route to the 5-ene. A detailed investigation into the photobromination of Beta-D-glucopyranose pentaacetate with bromine and with NBS led to the isolation of several by-products containing bromine substituents at C-1 and/or C-5; their reactions with zinc-acetic acid were studied, and the conformations. in solution of four alkenes derived from the 5-bromo compound were determined. 2,3,4-Triacylated 2,3,4,5-tetrahydroxycyclohexanones were Obtained by mercury (II) catalysed rearrangement of 5-deoxyhex-5-enopyranose esters. The mechanism of this rearrangement, and some enopyranose esters The mechanism of this rearrangement, reactions of the products were examined. The use of these new carbocyclic compounds in the synthesis of branched-chain cyclitol derivatives was explored. By means of diazomethane or, alternatively, hydrogen cyanide, substituted cyclohexanes with one-carbon branches and tertiary hydroxyl groups at the site of chain-branching were preared. Attempts to eliminate water from these tertiary alcohols to give substituted cyclohexene-carbonitriles or -carbaldehydes were unsuccessful.</p>

Synthesis of Functionalised Cyclohexanes from Carbohydrates

<p>Beta-D-glucopyranose pentaacetate was photobrominated to give the 5-baromide from which 6-deoxy-Beta-D-xylo-hex-5-enopyranose tetraacetate was obtained by reductive elimination. This reaction sequence represents an efficient new route to the 5-ene. A detailed investigation into the photobromination of Beta-D-glucopyranose pentaacetate with bromine and with NBS led to the isolation of several by-products containing bromine substituents at C-1 and/or C-5; their reactions with zinc-acetic acid were studied, and the conformations. in solution of four alkenes derived from the 5-bromo compound were determined. 2,3,4-Triacylated 2,3,4,5-tetrahydroxycyclohexanones were Obtained by mercury (II) catalysed rearrangement of 5-deoxyhex-5-enopyranose esters. The mechanism of this rearrangement, and some enopyranose esters The mechanism of this rearrangement, reactions of the products were examined. The use of these new carbocyclic compounds in the synthesis of branched-chain cyclitol derivatives was explored. By means of diazomethane or, alternatively, hydrogen cyanide, substituted cyclohexanes with one-carbon branches and tertiary hydroxyl groups at the site of chain-branching were preared. Attempts to eliminate water from these tertiary alcohols to give substituted cyclohexene-carbonitriles or -carbaldehydes were unsuccessful.</p>

DETERMINATION OF PROCESS RELATED GENOTOXIC IMPURITIES OF SALBUTAMOL SULPHATE BY LC METHOD

The main aim of this research work is to develop a suitable LC method for the quantitative determination of genotoxic impurities contains in Salbutamol Sulphate which is coming from the chemicals used during the manufacturing process. In manufacturing process many unwanted chemical materials are being used and out that many are following under Genotoxic category. After screening and doing the assessment on the genotoxic predication in salbutamol sulphate. The possible genotoxic impurities identified and likely to present in salbutamol Sulphate as Salicylic acid,[1][2][3] Acetyl methyl Salicylate (AMS),[4][5][6] Benzyl methyl salicylate (BMS),[7] Bromo-compound[8] and Dibromo-compound[8]. The main challenge is to separate all impurities from each other to get better resolution and response. As genotoxic[19][24] impurities estimation limit in final molecule is very minute and low it is not easy to quantify at ppm level present in Salbutamol sulphate in Active Pharmaceutical Ingredients. Hence the LC method was developed on Waters HPLC system (Water’s Ltd, USA) with 2995 UV detector at 273 nm as wavelength and 1.0 ml/min flow rate by using Spherical end-capped octylsilyl silica gel for chromatography (l = 0.15 m, Ø = 4.6 mm, 3µm) long with gradient system. The chromatographic and integrated data were recorded using Empower -3 data acquisition software. The limit of detection and the limit of quantitation for the impurity were established. Validation of the developed LC method was carried out as per ICH requirements and the data shows that the proposed method is specific, linear, accurate, precise and robust. This method has been tested in a number of Salbutamol Sulphate and used successfully for quantification of the reported impurities at ppm level. The developed LC method was found to be suitable to quantify the genotoxic impurities Salicylic acid, Acetyl methyl Salicylate (AMS), Benzyl methyl salicylate (BMS), Bromo-compound and Dibromo-compound at ppm level present Salbutamol Sulphate.

A Selective and Sensitive Method for Simultaneous Quantification of Genotoxic Impurities in Penciclovir drug substance and its dosage forms using UPLC-MS/MS

A selective, rapid and sensitive method was developed for the determination of genotoxic impurities (2-Amino-6-chloro purine and Bromo compound) in Penciclovir drug substance using RPUPLC-MS/MS. The chromatographic separation was performed on Kromasil C8 column (150 mm x 4.6 mm, 5 μm) maintained at 45°C using 0.1%formic acids in water as buffer and acetonitrile through gradient programme. The flow rate was maintained at 0.5mL/min with an injection volume of 10 μL. For the quantification of genotoxic impurities, positive-electrospray ionisation (ESI) mode was selected. Penciclovir and its impurities were well separated within the shortest run time of 16min. The chromatographic method was developed, and the results of all validation parameters showed that the technique is well confined to the limits of ICH guidelines. The method has high sensitivity, and the limit of detection was found to be as low as 0.15 and 0.30 ppm for 2-Amino-6-chloro purine and Bromo compound. The recovery of 2-Amino-6-chloro purine and Bromo compound are found in the range of 80-120%. The linearity of peak area versus concentration was demonstrated in the range of LOQ - 150% level of impurities with a correlation coefficient of 0.9999. The method has proved too robust by introducing minuscule changes in the chromatographic parameters. The method was successfully validated and applied for Penciclovir drug substances and their dosage forms to determine the mentioned genotoxic impurities.

Synthesis and reactions of 2-azido-1,3-di(benzyloxy)imidazolium hexafluoridophosphate

Abstract2-Azido-1,3-di(benzyloxy)imidazolium hexafluoridophosphate was obtained from the corresponding 2-bromo compound by reaction with sodium azide. Cycloaddition of the 2-azido compound with norbornene and norbornadiene gave the respective tricyclic aziridine and bicyclic azaoctadiene. Addition of triphenylphosphane yielded the phosphazide which upon heating eliminated dinitrogen to afford the phosphazene. The crystal structures of five compounds were determined by X-ray diffraction.

Synthesis of some Heterocyclic Compounds Derived from

The 4-(?-bromo acetyl)-4?-toluene sulfonanilide (2) was used as key intermediate to synthesize new heterocyclic compounds. This bromo compound was synthesized via sulfonation of amino group of p-amino acetophenone using Hinsburg method with 4-toluene sulfonyl chloride to form 4-acetyl-4?-toluene sulfonanilide (1) which is used as a starting material in this work. This compound was brominated to yield compound (2) which is used as a precursor to synthesize new five and seven membered heterocyclic compounds such as substituted 1,3-oxazoles (3,4), 1,3-thiazole derivatives (5-7), thiourea compounds (8a,b), 1,3-Thiazoline-2-thione compounds (9a-f) and 1,2,5-triazepine compounds (11a-d). The synthesized compounds were identified depending upon physical, FT-IR and UV spectroscopic data.

2-bromo-1-(2-hydroxyphenyI)-3,4-dimethyIpentan-1-one: A New Bromo-Compound with Stimulatory Activity Isolated from the Shed Leaves of Teak, (Tectona grandis L.)

A new Bromo isotopic compound has been isolated and purified from the Methanol Fraction of Teak leaves (MFTk). Chromatographic and spectral analyses (TLC, UV, MS, NMR, and IR) indicated the compound to be 2-bromo-1-(2-hydroxypheny1)-3, 4-dimethylpentan-1-one, in short, BrHPDMP with molecular weights 285 and 287. The whole leaf leachate of teak showed strong inhibitory activity in bioassay. But when fraction-4 (Methanolic fraction of teak leaf) was isolated and purified, it showed concentration dependent stimulatory activity on rice seeds. At 1000 ppm concentration, it showed 12.820% inhibition in shoot and 15.59% stimulation in root length. Below this concentration, it showed stimulatory effects on both shoot and root length. At 500ppm, it revealed 10.040% stimulation in shootlength and 34.16% stimulation in root length. At a concentration of 31.25ppm, it revealed maximum stimulatory effects i.e. 16.260% stimulation in shoot length and 42.78% stimulation in rootlength.

N-Heterocyclic Carbene (NHC) Derivatives of 1,3-Di(benzyloxy)imidazolium Salts

1-Hydroxyimidazole-3-oxide (1) was alkylated with benzyl bromide in the presence of NaHCO3 to give the new 1,3-di(benzyloxy)imidazolium bromide 2a which was converted to the hexafluorophosphate 2b and bis(trifluoromethylsulfonyl)imide 2c. From this cation, pyridine generated a carbene which was trapped by sulfur or selenium to yield the respective 2-thione 3 or 2-selone 4. Bromination afforded the 2-bromo derivative 5. Reaction of the hexafluorophosphate 2b with silver oxide gave the silver-N-heterocyclic carbene complex 6 which was transmetallated with Au(Me2S)Cl to the gold-carbene complex 7. A rhodium-carbene complex 8 was obtained by reaction of the hexafluorophosphate 2b with [Rh(cod)Cl]2 in the presence of triethylamine. Eight crystal structures were determined by X-ray diffraction. The N-benzyloxy groups are twisted out of the plane of the imidazole ring in the solid state. They adopt syn conformations in the cation of the hexafluorophosphate 2b and in the metal-carbene complexes 6 - 8, but anti conformations in the thione 3 and selone 4. Both conformations were observed in two polymorphs of the 2-bromo compound 5.

Polysulfonylamine, CLXXIX [1]. Intermolekulare Wechselwirkungen in kristallinen Di(organosulfonyl)aminen. Teil 4 [2]. Di(4-iodbenzolsulfonyl)amin und zwei Methylpyridinium-di(4-iodbenzolsulfonyl)amide: Iod-Sauerstoff vs. Iod-Iod-Wechselwirkungen / Polysulfonylamines, CLXXIX [1]. Intermolecular Interactions in Crystalline Di(organosulfonyl) amines. Part 4 [2]. Di(4-iodobenzenesulfonyl)amine and Two Methylpyridinium Di(4-iodobenzenesulfonyl) amides: Iodine-Oxygen vs. Iodine-Iodine Interactions

Low-temperature X-ray structures and crystal packing arrangements are presented for di(4-iodobenzenesulfonyl)amine (4, monoclinic, P21/c, Z ' = 1, isostructural to a previously described dimorph of the corresponding bromo homologue), 2,4-dimethylpyridinium di(4- iodobenzenesulfonyl)amide (5, monoclinic, P21/n, Z ' = 1, isostructural to the corresponding bromo compound), and 3-methylpyridinium di(4-iodobenzenesulfonyl)amide (6, orthorhombic, Pna21, Z '= 1). The packing of 4 consists of non-lamellar layers, in which the molecules are connected by N-H···O hydrogen bonds in one and by Iδ+···Oδ− interactions in the other dimension. Structure 5 involves strands of formula units, whereby the anions form catemers via Iδ+···Oδ− interactions and the cations are isotactically connected to the anion backbone by an N+-H(···O)2 three-centre bond. Short I···I contacts are absent from structures 4 and 5. In contrast, structure 6 displays lamellar layers comprising an inner lamella of cations and N(SO2)2 groups connected by an N+-H···N− two-centre bond, and peripheral regions of 4-iodophenyl rings. Thus, the iodine atoms are efficiently shielded from the oxygen atoms, but in appropriate positions to form Iδ+···Iδ− interlayer contacts. Each structure is reinforced by a parallel-displaced π···π stacking arrangement of aromatic rings and an abundance of short C-H···A contacts (A = acceptor).