Green synthesis of methadone in eutectic solvent

Eutectic solvents (DES), have attracted much attention in the last decade. With the advantages of nonflammability, thermal and chemical stability, high solubility and partial vapor pressure, non-toxicity and reasonable prices, these solvents are suggested as useful solvents. On the other hand, the eutectic solvents developed by Abbott are the new generation of ionic liquids. The mixture of eutectics is from an ammonium salt and a hydrogen bonding compound such as urea, acid, amine, and non-toxic amines. Choline chloride and urea, are quite environmentally friendly and are known practically as green solvents. The purpose of the present research is to present the synthesis of diphenyl acetonitrile with 1-dimethylamino-2-chloropropane by a eutectic’s solvent. In addition, methadone is synthesized from the reaction of 2,2-Diphenyl-4-dimethylaminovaleronitrile with ethyl magnesium bromide in the presence of solvent eutectic, which is in optimal and environmentally compatible conditions and by principles of green chemistry.

Magnesium Bromide (MgBr2) as a Catalyst for Living Cationic Polymerization and Ring-Expansion Cationic Polymerization

Magnesium bromide (MgBr2) was found as an effective catalyst for ring-expansion cationic polymerizations of isobutyl vinyl ether (IBVE) initiated by a “cyclic” hemiacetal ester (HAE) bond-based initiator leading to syntheses...

Synthesis of Spiro[cycloalkane-pyridazinones] with High Fsp3 Character Part 2.*

An extended compound library of spiro[cycloalkane-pyridazinones] with high Fsp3 character is targeted. There are two possibilities to improve the physicochemical parameters of a drug candidate molecules or building blocks, either to replace the aromatic systems with bioisoster heteroaromatic moieties, e.g. with one or two nitrogen containing ring systems (pyridines, pyridazines, pyrimidines, etc.), or to increase the Fsp3 character of the compounds. Using a new synthetic ap-proach, the Grignard reaction of 2-oxaspiro[4,5]decane-1,3-dione and 2-oxaspiro[4,4]nonane-1,3-dione with p-halophenyl- or p-alkylphenyl-magnesium bromide resulted in the formation of the corresponding 2-oxoethyl-cycloalkanecarboxylic ac-ids, which served as starting materials for the formation of pyridazinone with hydrazine or phenylhydrazine. The pyridazi-nones obtained were alkylated with methyliodide or benzylbromide. 16 Novel 4-tolyl- or 4-halophenyl-2,3-diazaspiro[5.5]undec-3-en-1-one and 4-tolyl- or 4-halopyhenyl-7,8-diazaspiro[4.5]dec-8-en-6-one, and their N-methyl, N-benzyl, and N-phenyl derivatives were synthetized.The physicochemical parameters and the Fsp3 character of the novel compounds obtained were studied. A few of them showed excellent logP and clogP values, but introduction of further phe-nyl group seemed to be disadvantageous

Continuous-Flow Synthesis of Tramadol from Cyclohexanone

A multioperation, continuous-flow platform for the synthesis of tramadol, ranging from gram to decagram quantities, is described. The platform is segmented into two halves allowing for a single operator to modulate between preparation of the intermediate by Mannich addition or complete the fully concatenated synthesis. All purification operations are incorporated in-line for the Mannich reaction. ‘Flash’ reactivity between meta-methoxyphenyl magnesium bromide and the Mannich product was controlled with a static helical mixer and tested with a combination of flow and batch-based and factorial evaluations. These efforts culminated in a rapid production rate of tramadol (13.7 g°h–1) sustained over 56 reactor volumes. A comparison of process metrics including E-Factor, production rate, and space-time yield are used to contextualize the developed platform with respect to established engineering and synthetic methods for making tramadol.

Novel Synthesis of β-Keto Cycloacetals via Organoboranes

(Z)-1-Bromo-1-alkenylboronate esters were easily synthesized from the hydroboration of terminal alkynes with dibromoborane dimethyl complex under nitrogen atmosphere followed by treatment with propne-1,3-diol. These boronate esters are readily reacted with 1,3-dioxan-2-ylethyl)magnesium bromide in ether and tetrahydrofuran at -78 ºC for 1 h. The resulting "ate" complex upon addition of sodium methoxide in methanol undergo intramolecular nucleophilic substitution reactions to produce the corresponding (E)-alkenylboronate esters containing (1,3-dioxan-2-ylethyl) moiety in 70-82% isolated yields. The resulting intermediates are oxidized with sodium acetate and hydrogen peroxide to provide the corresponding β-keto cycloacetals in good yields (68-84%).

Pressure-induced unexpected −2 oxidation states of bromine and superconductivity in magnesium bromide

Upon compression, three unusual stoichiometries are predicted. The Br exhibits an oxidation state of −2 in I4/mmm Mg4Br and Pm3̄m MgBr phases. Moreover, the I4/mmm Mg4Br behave as a typical electride and P21/m-MgBr3 is predicted as superconductor.