Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters

• Satish S. More,
• T. Krishna Mohan,
• Y. Sateesh Kumar,
• U. K. Syam Kumar and
• Navin B. Patel

Beilstein J. Org. Chem. 2011, 7, 831–838, doi:10.3762/bjoc.7.95

• -chloromethylene)malonates 19. The chloro alkenyl malonates 19 were synthesized in two steps from diethyl malonate and acid chlorides. The acylation of diethyl malonate was carried out with various acyl chlorides in the presence of anhydrous magnesium chloride and triethylamine, as per the reaction conditions

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• chloride 89 are added concurrently from two different sides of the reactor to stop these reagents reacting with each other. This method of adding the reagents circumvents the necessity to isolate the magnesium salt of the indole and increases the yield from 50 to 82%. The carbonyl group of the proline side

Oxidative allylic rearrangement of cycloalkenols: Formal total synthesis of enantiomerically pure trisporic acid B

• Silke Dubberke,
• Muhammad Abbas and
• Bernhard Westermann

Beilstein J. Org. Chem. 2011, 7, 421–425, doi:10.3762/bjoc.7.54

• cyclohexenone (+)-7, which is the key building block in our synthesis, was the incorporation of a C2 unit into β-ketoester (−)-1c (Scheme 3). This was achieved by adding ethynyl magnesium bromide in THF at room temperature. The cyclohexenol (+)-6 can be isolated in 79% yield with a diastereomeric ratio of 96:4

• -dimethylcyclohex-3-ene-1-carboxylate (6). To a solution of (−)-1c (0.50 g, 2.75 mmol) in THF (5 mL), was added dropwise over a period of 30 min ethynyl magnesium bromide (0.5 M in THF; 9.05 mL, 4.53 mmol) at 20 °C. Stirring at this temperature was continued for 1 h, and then the reaction mixture was quenched by

Anion–π interactions influence pK_a values

• Christopher J. Cadman and
• Anna K. Croft

Beilstein J. Org. Chem. 2011, 7, 320–328, doi:10.3762/bjoc.7.42

• heated (110 °C, 19–43 h, Table 4) then left to cool and extracted twice with diethyl ether (25 cm3) and water (25 cm3), and once with brine (25 cm3). The extracts were dried with magnesium sulfate. The products (1–5) were isolated by column chromatography on silica gel with hexane/ethyl acetate as the

Reciprocal polyhedra and the Euler relationship: cage hydrocarbons, C_nH_n and closo-boranes [B_xH_x]²⁻

• Michael J. McGlinchey and
• Henning Hopf

Beilstein J. Org. Chem. 2011, 7, 222–233, doi:10.3762/bjoc.7.30

• by sodium- or magnesium-mediated dehalogenation of the appropriate REX3 precursor, where R is a very bulky alkyl or aryl group, and X is chlorine or bromine [38][39]. The hexatellurium cation, [Te6]4+, is also trigonal prismatic [40][41]. Similarly, the inorganic cubane analogues R8E8, where E = Si

Photocycloaddition of aromatic and aliphatic aldehydes to isoxazoles: Cycloaddition reactivity and stability studies

• Axel G. Griesbeck,
• Marco Franke,
• Jörg Neudörfl and
• Hidehiro Kotaka

Beilstein J. Org. Chem. 2011, 7, 127–134, doi:10.3762/bjoc.7.18

• , extracted two times with chloroform, dried over magnesium sulfate and filtered. The solvent was evaporated and the residual oil distilled (170 °C) to give 23.01 g (72%) of 3 as a colorless oil. 13C NMR (75.5 MHz, CDCl3): 204.8 (2C, Cq), 190.1 (1C, Cq), 104.5 (1C, Cq), 61.4 (1C, CH), 28.4 (2C, CH3), 23.0 (1C

• organic layers were neutralized with aqueous sodium hydroxide. The organic solution was then washed two times with water, dried over magnesium sulfate, filtered and evaporated. The resulting solid was recrystallized twice from ethanol to yield 6.34 g (41%) of 4 as colorless crystals. 13C NMR (75.5 MHz

• hydrochloride (5.56 g, 80 mmol), potassium carbonate (5.53 g, 40 mmol), ethanol (40 mL) and water (40 mL) was stirred at rt for 15 h. The solid was filtered, washed with water and extracted three times with ether. The combined organic layers were dried over magnesium sulfate, filtered and the solvent was

Redox-active tetrathiafulvalene and dithiolene compounds derived from allylic 1,4-diol rearrangement products of disubstituted 1,3-dithiole derivatives

• Filipe Vilela,
• Peter J. Skabara,
• Christopher R. Mason,
• Thomas D. J. Westgate,
• Asun Luquin,
• Simon J. Coles and
• Michael B. Hursthouse

Beilstein J. Org. Chem. 2010, 6, 1002–1014, doi:10.3762/bjoc.6.113

• ) and re-extracted with dichloromethane or ethyl acetate (3 × 100 cm3). The combined extracts were dried over magnesium sulfate and the solvent removed under reduced pressure. All compounds were purified by column chromatography (silica). 4,6-Diphenyl-4,6-dihydro-[1,3]dithiolo[4,5-c]furan-2-thione (5

• ), dried over magnesium sulfate and filtered. The solvent was removed under reduced pressure to yield a straw-coloured solid which was purified by recrystallisation from dichloromethane and petroleum ether 40/60, to give 26 as straw needles, 0.145 g, 89%, mp 118–124 °C; EI+ MS (M+) 306; Accurate mass

• added and the reaction stirred at room temperature for 16 h, during which time a white precipitate formed. The mixture was added to water (50 ml) and extracted with dichloromethane (3 × 100 ml). The combined organic extracts were dried over magnesium sulfate, filtered, and the solvent was removed under

Chain stopper engineering for hydrogen bonded supramolecular polymers

• Thomas Pinault,
• Bruno Andrioletti and
• Laurent Bouteiller

Beilstein J. Org. Chem. 2010, 6, 869–875, doi:10.3762/bjoc.6.102

• mmol) in dry THF (100 mL) was then added, and the solution heated under reflux for 24 h. After cooling, ice was slowly added and the solvent evaporated. Chloroform (200 mL) was added and the organic phase washed successively with brine (300 mL) and water (2 × 300 mL), dried over magnesium sulfate and

• over magnesium sulfate and concentrated. Silica gel column chromatography (ethyl acetate/dichloromethane and then ethyl acetate) followed by recrystallization from pentane afforded 0.66 g of a white solid (57%). 1H NMR (200 MHz, DMSO-d6): δ (ppm) = 7.42/7.17 (2d, 4H, Ar-H), 3.21 (m, 6H, N-CH2), 2.15 (s

Novel 2-(ω-phosphonooxy-2-oxaalkyl)acrylate monomers for self-etching self-priming one part adhesive

• Joachim E. Klee and
• Uwe Lehmann

Beilstein J. Org. Chem. 2010, 6, 766–772, doi:10.3762/bjoc.6.95

• ) 1,2-ethanediol. After stirring for 12 h at room temperature, the solution was washed successively with 1 × 200 mL water, 2 × 250 mL of an aqueous sodium carbonate solution (25 wt %) and 1 × 200 mL water. The organic layer was dried over magnesium sulfate and filtered. After the evaporation of the

• . The layers were separated and the aqueous layer was washed with 2 × 100 mL diethyl ether. The aqueous layer was reduced in volume to 100 mL and extracted with 4 × 100 mL dichloromethane. The combined organic extracts were dried over magnesium sulfate, filtered and evaporated to yield 19 g of a yellow

Synthesis of 5-(6-hydroxy-7H-purine-8-ylthio)- 2-(N-hydroxyformamido)pentanoic acid

• Yanmei Zhang,
• Greg Elliot,
• Adrian Saldanha,
• Igor Tsigelny,
• Dennis Carson and
• Wolf Wrasidlo

Beilstein J. Org. Chem. 2010, 6, 742–747, doi:10.3762/bjoc.6.93

• a nucleoside. A prototype compound was designed and docked into the catalytic domain of the AdSS enzyme bridging the region between the magnesium center of the protein to the nucleoside region. The synthesis involves coupling a brominated peptide fragment capable of complexing magnesium to a

• reaction mixture was stirred at −78 °C for 5 min, and then at 0 °C for 1 h. Saturated ammonium chloride solution (15.0 mL) was added and the mixture extracted three times with ethyl acetate. The combined ethyl acetate extracts were washed successively with water and brine, dried with magnesium sulfate and

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

• chlorination with only minor amounts of bis-(CF3S) products (Scheme 12). Aryl magnesium [78] and -mercury [79] compounds have been employed for the introduction of CF3S groups. Such reactions proceed in ether or THF at low temperatures; however, the yields of aryltrifluoromethyl sulfides do not exceed 50–60

Kinetic studies and predictions on the hydrolysis and aminolysis of esters of 2-S-phosphorylacetates

• Milena Trmčić and
• David R. W. Hodgson

Beilstein J. Org. Chem. 2010, 6, 732–741, doi:10.3762/bjoc.6.87

• layers were separated, and the organic layer was washed successively with water (2 × 5 mL), hydrochloric acid (0.1 M, 3 × 5 mL) and saturated sodium chloride solution (5 mL). The organic phase was then dried over anhydrous magnesium sulphate and the solvent removed under reduced pressure to give the p

Recent advances in carbocupration of α-heterosubstituted alkynes

• Ahmad Basheer and
• Ilan Marek

Beilstein J. Org. Chem. 2010, 6, No. 77, doi:10.3762/bjoc.6.77

• (−40 instead of −78 °C), which can be attributed to a slow copper to magnesium contrathermodynamic transmetalation reaction, probably due to a strong intramolecular chelation of the sp2 organometallic derivative by the carbamate moiety. N-substituted alkynes Nitrogen-substituted alkynes (ynamine

• carbometalation of 1-alkynylphosphines with magnesium dibutylcuprate (Bu2CuMgBr) leads to diphenyl(butylethynyl)phosphine in good isolated yields [29][30]. The addition of various electrophiles (with the exception of aldehydes and methyl iodide) such as allylbromide, benzoyl chloride) was successful (Scheme 14

• α-sulfinyl vinylcopper and zinc intermediates, 36 and 37 respectively, retain their geometry at room temperature is in sharp contrast to α-sulfinyl vinyllithium- or magnesium species that isomerize to the thermodynamically more stable geometric isomer at low temperature. When an enantiomerically

Synthesis, electronic properties and self-assembly on Au{111} of thiolated (oligo)phenothiazines

• Adam W. Franz,
• Svetlana Stoycheva,
• Michael Himmelhaus and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2010, 6, No. 72, doi:10.3762/bjoc.6.72

• dried with magnesium sulfate and the solvents removed in vacuo. The residue was chromatographed on silica gel (hexane/acetone 50:1) to give 1.53 g (36%) of 1e as a yellow resin. 1H NMR (300 MHz, CD2Cl2): δ = 0.76–0.81 (m, 12H), 1.18–1.26 (m, 16H), 1.30–1.40 (m, 8H), 1.63–1.75 (m, 8H), 3.69–3.77 (m, 8H

• . The solution was allowed to come to room temperature and stirred overnight. Then, 50 mL of water was added and the aqueous phase was extracted several times with small portions of dichloromethane. The combined organic phases were dried with magnesium sulfate and the solvents removed in vacuo. The

• allowed to come to room temperature and stirred overnight. Then, 50 mL of water was added and the aqueous phase extracted several times with small portions of dichloromethane. The combined organic phases were dried with magnesium sulfate and the solvents removed in vacuo. The residue was chromatographed

Acid catalyzed cyclodimerization of 2,2-bis(trifluoromethyl)-4-alkoxy-oxetanes and -thietanes. Synthesis of 2,2,6,6-tetrakis(trifluoromethyl)-4,8-dialkoxy-1,5-dioxocanes and 3,3,7,7-tetrakis(trifluoromethyl)-9-oxa-2,6-dithia-bicyclo[3.3.1]nonane

• Viacheslav A. Petrov and
• Will Marshall

Beilstein J. Org. Chem. 2010, 6, No. 46, doi:10.3762/bjoc.6.46

• C2H5O) include the formation of 4-(4,4-bis(trifluoromethyl)thietan-2-yloxy)-2,2-bis(trifluoromethyl)thietane on treatment with H2SO4 [4], thiophilic ring opening by the action of alkyl magnesium or lithium reagents [4], the recently reported oxidation with selective formation of the corresponding S

Efficient and improved synthesis of Telmisartan

• A. Sanjeev Kumar,
• Samir Ghosh and
• G. N. Mehta

Beilstein J. Org. Chem. 2010, 6, No. 25, doi:10.3762/bjoc.6.25

• iodides 5 and 6 using 5 equiv of copper [7]. Modern syntheses of 7 involve cross-couplings of sensitive aryl magnesium [8], zinc [9], or boron [10][11] compounds with alkyl 2-halobenzoates. Since the commercialization of Telmisartan, 7 has become readily available at low cost, so that most subsequent

A short synthesis of (±)-cherylline dimethyl ether

• Bhima Y. Kale,
• Ananta D. Shinde,
• Swapnil S. Sonar,
• Bapurao B. Shingate,
• Sanjeev Kumar,
• Samir Ghosh,
• Soodamani Venugopal and
• Murlidhar S. Shingare

Beilstein J. Org. Chem. 2009, 5, No. 80, doi:10.3762/bjoc.5.80

• leaving a colorless solution, which was dried over anhydrous magnesium sulfate. Removal of the solvent under reduced pressure produced acyl azide. Curtius rearrangement. The acyl azide was dissolved in dry toluene (30 mL) and heated to reflux for 1 h. Concentration of reaction mixture under vacuum gave

An enantiomerically pure siderophore type ligand for the diastereoselective 1 : 1 complexation of lanthanide(III) ions

• Markus Albrecht,
• Olga Osetska,
• Thomas Abel,
• Gebhard Haberhauer and
• Eva Ziegler

Beilstein J. Org. Chem. 2009, 5, No. 78, doi:10.3762/bjoc.5.78

• mg, 1.20 mmol) and 3 (200 mg, 0.62 mmol). The solution was heated and refluxed for 12 h. After cooling to room temperature the solution was stirred 12 h and afterwards concentrated to dryness. The residue was dissolved in ethyl acetate, washed with water and brine and dried with anhydrous magnesium

Preparation and Diels–Alder/cross coupling reactions of a 2-diethanolaminoboron- substituted 1,3-diene

• Liqiong Wang,
• Cynthia S. Day,
• Marcus W. Wright and
• Mark E. Welker

Beilstein J. Org. Chem. 2009, 5, No. 45, doi:10.3762/bjoc.5.45

• boronate 2: A mixture of magnesium (1.0 g, 41.1 mmol), 1,2-dibromoethane (0.5 mL), and THF (10 mL) was refluxed under nitrogen for 15 min to activate the magnesium. To the mixture anhydrous zinc chloride (0.6 g) in THF (60 mL) was added and reflux was continued for another 15 min. 2-Chloro-1,3-butadiene

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

Controlling hazardous chemicals in microreactors: Synthesis with iodine azide

• Johan C. Brandt and
• Thomas Wirth

Beilstein J. Org. Chem. 2009, 5, No. 30, doi:10.3762/bjoc.5.30

• (30 mL). Then tetrabutylammonium hydroxide (100 mmol, 26 g) was added and the mixture was stirred at room temperature for 90 min. Dichloromethane (50 mL) was added and stirring was continued for 10 min. The organic layer was separated and dried over magnesium sulfate. Finally the solvent was removed

• was terminated at the outlet with 5 mol% aq thiosulfate solution. For work-up, the mixture was extracted with dichloromethane (3 × 10 mL). The combined organic phases were separated, dried over magnesium sulfate and the solvent removed under reduced pressure. Phenylcarbamoyl azide (4a) The crude

• . The mixture was then diluted with AcOH/THF (20 mL/20 mL) and aq sodium carbonate (20 mL). Then ethylacetate (60 mL) was added, the organic layer separated and dried over magnesium sulfate. The crude product was purified with a silica gel column using hexane/CH2Cl2 15:1 as eluent. Yield: 14 mg (quant

From discovery to production: Scale- out of continuous flow meso reactors

• Peter Styring and
• Ana I. R. Parracho

Beilstein J. Org. Chem. 2009, 5, No. 29, doi:10.3762/bjoc.5.29

• less reactive, as the waste magnesium chloride or mixed halide was more soluble in THF under the reaction conditions than magnesium bromide and this prevented significant build up of the salt in the reactor while in use, which would otherwise lead to blockage. Batch reactions were performed in order to

• study the possibility of catalyst deactivation was considered. However, the fact that steady state production of around 66% over the study up to 31 h would dispel this theory. Indeed ICP-AES studies showed no significant loss of nickel from the catalyst. The likely scenario is that magnesium salts had

Synthesis of rigidified flavin–guanidinium ion conjugates and investigation of their photocatalytic properties

• Harald Schmaderer,
• Mouchumi Bhuyan and
• Burkhard König

Beilstein J. Org. Chem. 2009, 5, No. 26, doi:10.3762/bjoc.5.26

• ) at 0 °C. The mixture was stirred at room temperature for 20 h, diluted with CHCl3 (150 mL) and washed with brine twice. The organic phase was separated, dried over magnesium sulfate and the solvents were evaporated to yield an orange solid. The crude product was purified by flash column

• for 20 h, diluted with CHCl3 (250 mL) and washed with water and brine. The organic phase was separated, dried over magnesium sulfate and the solvents were evaporated. The crude brown product was purified by flash column chromatography (CHCl3:MeOH:N(Et)3 – 70:1:1). Yield: 564 mg, 798 μmol, 82%, yellow

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• used in the total synthesis of mucocin (Scheme 21) [65]. The ylide 149, which was synthesized from the cis-THF alcohol 148a, was coupled with the butenolide aldehyde 150 via a Wittig reaction to afford the THF aldehyde 151 after further 3 steps. Then addition of the magnesium derivative of iodide 152

Convenient method for preparing benzyl ethers and esters using 2-benzyloxypyridine

• Susana S. Lopez and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2008, 4, No. 44, doi:10.3762/bjoc.4.44

• excellent yield by in situ methylation of 2-benzyloxypyridine in the presence of alcohols and magnesium oxide. This simple protocol extends to the synthesis of other arylmethyl ethers and esters. Toluene is a suitable solvent for most applications, although trifluorotoluene is required in at least one case

• -benzyloxypyridine (2), and magnesium oxide in toluene was cooled to 0 °C and treated with methyl triflate. The reaction mixture was allowed to warm to room temperature and then heated at 90 °C for 24 h. Table 1 summarizes the results from the benzylation of a representative group of functionalized alcohols under

• in a related system is associated with sulfonic acid-catalyzed arylmethylation reactions [35]. Therefore, methyl triflate is recommended for promoting the arylmethylation of alcohols under the neutral, magnesium oxide-buffered conditions reported herein. Conclusion A new protocol for the synthesis of