6-(substituted phenyl)-5-methyl-4,5-dihydro-pyridazin-3(2H)-ones of medicinal interest. The synthesis of SK&F 94836 and SK&F 95654

Two synthetic routes to the dihydropyridazinone-cyanoguanidine 4 (SK&F 94836) are described, both proceeding via the anilino compound 6. An efficient synthesis of the dihydropyridazinone-pyridone 5 (SK&F 95654) is reported. This synthesis proceeds via the fluoro-keto-acid 24 , with subsequent displacement of the fluoro substituent by 4-pyridone. The surprising effectiveness of water as a solvent in this reaction has been highlighted.     

Novel dissolution procedure using a mixture of manganese dioxide and hydrochloric acid for the matrix-independent determination of gold

 A mixture of manganese dioxide and hydrochloric acid has been used for the accurate and precise determination of gold in various gold-bearing matrices. Results of intermethod comparison studies, F-test on variances, Mann-Whitney U-test, Spearman rank correlation and regression analyses are presented. The recommended method can be applied to a quality control programme and for the evaluation of reference materials. Various standard reference materials (SRM) of diverse matrices have been examined to check the validity of the method and the results were found to be in very good agreement with the certified data. Sample decomposition is straight forward [1–10 g sample (roasted at 600–700 °C)+5 g of MnO₂+30 mL of 2 mol/L HCl]. Gold is coprecipitated with potassium tellurite using tin (II) chloride solution. The precipitate is extracted into toluene and finally stripped back into aqua-regia solution for final nebulization into an air-acetylene flame for atomic absorption spectrophotometry. The method is very simple and easily adaptable, and more convenient than conventional methods involving aqua regia or a hydrobromic acid-bromine water mixture. Received: 23 October 1995/Revised: 18 March 1996/Accepted: 23 March 1996     

The effect of ultrasound on the solvolysis of 2-chloro-2-methylpropane in aqueous ethanol

Ultrasonic irradiation has been found to accelerate the solvolysis of 2-chloro-2-methylpropane in aqueous ethanol mixtures from 20 to 60% w/w in ethanol at temperatures between 10° and 25°. The effects are more marked at lower temperatures and higher alcohol compositions with a 20 fold rate acceleration occurring at 10° and 60% w/w. The results also lend independent support to two previous observations that (a) the position of maximum in solvent structuredness is 50% w/w and (b) a logarithmic relationship exists between solvent vapour pressure and ultrasonically enhanced rate constant. At solvent compositions of 50 and 60% w/w ethanol the absolute rate of reaction under irradiation increases with decreasing reaction temperature below 20°.     

Synthesis of the Thiazolone Analogue of the Acetylcholinesterase Inhibitor,Huperzine A

The preparation of an analogue 3a of the acetylcholinesterase inhibitor, huperzine A ( 1 ), is described in which the pyridinone moiety of the natural product is replaced with a thiazolone moiety. The synthesis started from cyclohexane-1,4-dione monoethylene ketal ( 7 ) by first annulating the thiazole ring using the Gewald protocol (→ 8 ; Scheme 1) and then constructing the bicyclo[3.3.1]nonane substructure using our previously described Michael addition/aldol condensation methodology (Scheme 3). The central problem was the protection of the thiazolone carbonyl group; only the 2-unsubstituted thiazole survived the reaction conditions of the first half of the synthesis. Refunctionalization was later effected by lithiation and subsequent chlorination with hexachloroethane ( 30→31 ). Compound 3a was ineffective in the acetylcholinesterase inhibition assay in concentrations up to 14 μM .     

One-pot two-step synthesis of 4-vinylphenols from 4-hydroxy substituted benzaldehydes under microwave irradiation: a new perspective on the classical Knoevenagel-Doebner reaction

The classical Knoevenagel-Doebner reaction is reinvestigated wherein the direct synthesis of substituted 4-vinylphenols instead of the expected 4-hydroxycinnamic acids is described. The condensation reaction is performed on 4-hydroxy substituted benzaldehydes and malonic acid with a mixture of acetic acid-piperidine as condensing agent under focused microwave irradiation. The occurrence of simultaneous condensation-double decarboxylation without the use of any decarboxylating agent is a new finding, the reaction being facilitated solely by the hydroxy substituent and microwave irradiation effect.     

Efficient one-pot, two-step synthesis of (E)-cinnmaldehydes by dehydrogenation-oxidation of arylpropanes using DDQ under ultrasonic irradiation

A general, efficient and new approach to the synthesis of cinnamaldehydes with trans-selectivity has been accomplished starting from arylpropanes. One-pot, two-step dehydrogenation and oxidation of arylpropanes with excess DDQ in dioxane containing a few drops of acetic acid gave (E)-cinnmaldehydes under ultrasound irradiation.     

Technical and economic evaluation of different reactors for methanotrophic cultures for propylene oxide production

A two-stage process for the manufacture of propylene oxide is described. The preliminary economics based on use of methanol as a regeneration factor has resulted in a production cost of $12.10/lb of propylene oxide based on propylene oxide production rate of 40 mg/g-cell/h in conventional reactor. Increasing the propylene oxide production from 40 to 500 mg/g-cell/h resulted in a cost reduction from $12.10 to 5.8/lb of propylene oxide. The granular-activated, carbon-fluidized bed reactor (GAC-FBR) absorbs the propylene oxide and when saturated is eluted with ethyl acetate, and the bed is regenerated by steam to drive off the residual solvents. The estimated manufacturing costs are approx 59% lower (from $12.10/lb in conventional reactors to $5.00/lb for GAC-FBRs) for products that are highly inhibitory such as epoxides. In the GAC-FBR reactor, enhancing the propylene oxide production rate from 120 to 1500 mg/gcell/h has resulted in the cost reduction to $2.00/lb. Enhancing the production capacity from 1 million lb to 10 million lb/yr has further reduced the cost of production to $1.00/lb. This article is reprinted from the Symposium issue of ABAB entitled “Biotechnology for Fuels and Chemicals: Proceedings of the Nineteenth Symposium of Biotechnology for Fuels and Chemicals” (pp. 651–659). Figures and captions are correct as they now appear.