Rosenmund-von Braun Reaction Research Articles

Total synthesis of natural benzoazepinoquinolinone alkaloid irrepairzepine via Au(I)-catalyzed cycloisomerization and regioselective functionalization

Irrepairzepine (1), a unique benzoazepinoquinolinone alkaloid isolated from an endophytic fungus, exhibits synthetic lethality targeting in PTEN-deficient glioblastoma cells. Herein, the first synthesis of irrepairzepine was achieved through a series of high-yielding reactions. The key steps include the synthesis of quinoline via the Au(I)-catalyzed cycloisomerization of N-propargyl aniline and construction of the azepinone core through the acid-catalyzed lactamization of an aminophenyl cyanoquinoline precursor, which was prepared using a simple umpolung approach that involves regioselective bromination followed by the Rosenmund-von Braun reaction.

Expedient, regioselective C-H chalcogenation of 3,4-dihydro-1,4-benzoxazines using a palladium-copper catalyst.

The palladium-catalysed regioselective C-H chalcogenation of benzoxazines with disulfides and diselenides in air has been described. In this protocol, palladium acetate serves as the catalyst in conjunction with copper as an oxidizing agent. Through this approach, a wide array of sulfenylation and selenylation reactions of benzomorpholines have been effected, yielding results ranging from good to excellent. Thus, the established procedure demonstrates superb regioselectivity and a strong tolerance towards various functional groups and is suitable for gram-scale synthesis. Additionally, this synthetic approach offers a practical and convenient pathway for late-stage functionalization leading to the Rosenmund-von Braun reaction.

Ligand-Promoted Rosenmund–von Braun Reaction

AbstractTwo picolinamide ligands were found to have significant accelerating effect to classical Rosenmund–von Braun reaction, making the coupling of (hetero)aryl bromides with CuCN occur at 100–120 °C with good to excellent yields in most cases. A large number of functional groups and heterocycles were tolerated under these conditions, thereby providing a convenient and reliable approach for diverse synthesis of aryl nitriles.

Electron-Transfer Driven Cyanation of Aryl Iodides

Aryl cyanides are widely utilized as important intermediates in the research fields of pharmaceuticals, natural products and also organic materials, because the nitrile group can easily be transformed into a wide variety of functional groups, such as amides, carboxylic acids, imines, ketones, and amines. In the preparation of aryl cyanides, Rosenmund–von Braun reaction, in which an aryl halide reacts with copper cyanide, is often used; however, harsh reaction conditions are required, and the separation of cupper complexes in a workup process is often problematic, especially in a large-scale synthesis. We initiated our study to develop a copper free method to prepare aryl cyanides, and found that a catalytic amount of 1,10-phenanthroline nicely promoted the reaction of aryl iodides with tetraethylammonium cyanide to afford aryl cyanides (Scheme 1). 1,10-phenanthroline would work as a SET initiator on the first stage to generate radical anion. We next tried to use the electrochemical reaction for the initiation step. Electricity was simply passed to the mixed solution of aryl iodides and tetraethylammonium cyanide to afford the corresponding aryl cyanides in moderate yields. Notably, the reactions proceeded with a catalytic amount of electricity. Figure 1

Heterocyclic analogs of 5,12-naphthacenequinone 15*. Synthesis of new anthra[2,3-b]thiophene-3(2)-carboxylic acids

Methods have been developed for the synthesis of anthra[2,3-b]thiophene-3(2)-carboxylic acids and their derivatives through modifications of 4,11-dibutoxy-3-methylanthra[2,3-b]thiophene-5,10-dione. A scheme involving methyl group transformations was proposed for the preparation of dibutoxyanthra[2,3-b]thiophene-3-carboxylic acid, including reactions of radical halogenation, hydrolysis, and oxidation of a 3-formyl derivative. 4,11-Dihydroxy-3-methylanthra[2,3-b]thiophene-2-carboxylic acid was synthesized from the appropriate carbonitrile, obtained by Rosenmund–von Braun reaction from 2-bromo-4,11-dibutoxy-3-methylanthra[2,3-b]-thiophene-5,10-dione.

Regio-selective cyanation of (Z)-(1,2-dibromo-2-arylvinyl)triisopropylsilane with suppression of halogen elimination

Highly regio-selective cyanation of vicinal (Z)-dibromoalkenyl silanes was achieved by a vinylic Rosenmund-von Braun reaction, significantly suppressing side-production of alkyne. The alkyne was generated by a halogen elimination side-reaction that is an intrinsic problem in metal-activation of vicinal dihaloalkenes. We have studied to overcome the problem, and finally found the combination of CuCN and O=PPh3 in toluene solvent effectively controlled the production of byproducts. The resultant single isomer has significance in potentially application as a multi-tunable synthetic scaffold.

Elucidation of reaction process through β-halogen elimination in CuCN-mediated cyanation of (E)-1-bromo-2-iodoalkene

The previously unknown reaction process involved with metal-mediated β-halogen elimination is described, including a description of a vinylic Rosenmund–von Braun reaction of (E)-(1-bromo-2-iodobut-1-en-1-yl)benzene. We investigated the product structures on the basis of crystallographic analyses and revealed that copper cyanide would form bifurcated paths to deliver the isomeric mixtures.

A vinylic Rosenmund-von Braun reaction: practical synthesis of acrylonitriles.

An efficient system based on acetone cyanohydrin and catalytic amounts of copper(I) iodide and 1,10-phenanthroline is reported for the cyanation of alkenyl iodides. A wide range of polysubstituted acrylonitriles could be obtained in fair to good yields and with complete retention of the geometry of the double bond. This extension of the Rosenmund-von Braun reaction also enabled a straightforward formal synthesis of the naturally occurring acrylonitrile alliarinoside.

Tetraimidazophthalocyanines: influence of protonation and aggregation on spectroscopic observations

The synthesis and spectroscopic characterization of tetraimidazophthalocyanines are presented. This kind of molecules have not been intensively studied due to difficulty in (i) obtaining an easily obtainable synthon: a benzimidazole ring with a variety of substituent, and (ii) achieving the Rosenmund-Von Braun reaction with good yields. The synthesis of novel 2-substituted-5,6-dicyanobenzimidazoles (4a–e) achieved from 4,5-dibromo-N,N'-diacetylated-1,2-phenylene diamine (2a–e) or 2-substituted-5,6-dibromobenzimidazole (3a–e) were optimized. Depending on the starting compound, the reaction could be done according to a two-step pathway (cyclization followed by nitrilation) or a one-pot procedure using microwave irradiation. The target compounds, tetraimidazophthalocyanines (ImiPc(M)) (5a–e;6a–d), were prepared. The effect of the four imidazoles introduced in the phthalocyanines core were compared and discussed.

L-Proline-Promoted Rosenmund-von Braun Reaction

l-Proline was identified as an effective additive to promote the Rosenmund-von Braun reaction at a lower temperature (80-120 °C). This modified Rosenmund-von Braun cyanation of aryl bromides exhibits excellent functional-group compatibility, and provide an efficient and convenient approach for the synthesis of aryl nitriles.

A Practical Synthesis of Highly Functionalized Aryl Nitriles Through Cyanation of Aryl Bromides Employing Heterogeneous Pd/C: In Quest of an Industrially Viable Process.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A practical synthesis of highly functionalized aryl nitriles through cyanation of aryl bromides employing heterogeneous Pd/C: in quest of an industrially viable process

Preparation of aryl nitrile 2a through classical Rosenmund-von Braun reaction of aryl bromide 1a resulted in a poor yield (61%) due to a high reaction temperature (165 °C) and a lack of efficient procedure for separating 2a from a large quantity of heavy metal waste (Cu salts). To address these issues, a practical synthesis of multifunctional aryl nitriles through cyanation of aryl bromides has been developed with heterogeneous Pd/C used as the catalyst. Treatment of aryl bromides 1 with Zn(CN) 2 in the presence of Pd/C, Zn, ZnBr 2 and PPh 3 in DMA provided aryl nitriles 2 involving those carrying sterically demanding electron-rich substituent in good yields and in highly reproducible manner. The activity of Pd/C is highly dependent on the properties of the Pd/C. Oxidic thickshell type catalyst Pd/C D5 was found to furnish the highest rate acceleration and yield. The use of heterogeneous Pd/C might anchor and disperse Pd over the solid support of the catalyst, at least in the initial stage of the reaction, to assure the formation of monomeric Pd complex without precipitating to inactive Pd black. The use of a slightly excess of Zn(CN) 2 (0.6 equiv) and air oxidation of phosphine ligand, after end of the reaction, converted Pd species to insoluble phosphine-free Pd cyanides, from which Pd was recovered in high yield through simple filtration followed by usual recovery process involving combustion.

Efficient Microwave‐Assisted Cyanation of Aryl Bromide

Aryl nitriles were easily prepared from the corresponding bromides and copper cyanide in good yields through microwave‐accelerated Rosenmund–von Braun reaction in N‐methylpyrrolidinone (NMP) under ambient pressure.

Efficient Microwave‐Assisted Cyanation of Aryl Bromide.

AbstractFor Abstract see ChemInform Abstract in Full Text.

High yield synthesis of aryl cyanides under microwave irradiation

Reaction of anhydrous cuprous cyanide with aryl bromides produced aryl cyanides (Rosenmund–von Braun reaction) under microwave irradiation in a short time and in high yield.

Copper‐Catalyzed Domino Halide Exchange‐Cyanation of Aryl Bromides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Copper-catalyzed domino halide exchange-cyanation of aryl bromides.

An efficient copper-catalyzed domino halogen exchange-cyanation procedure for aryl bromides was developed utilizing 10 mol % CuI, 20 mol % KI, 1.0 equiv of the inexpensive N,N'-dimethylethylenediamine as ligand, and 1.2 equiv of NaCN in toluene at 110 degrees C. The new method represents a significant improvement over the traditional Rosenmund-von Braun reaction: the reaction conditions are much milder, and the use of stoichiometric amounts of copper(I) cyanide and polar solvents is avoided; therefore the isolation and purification of the aromatic nitrile products is greatly simplified. In addition, the new method exhibits excellent functional group compatibility comparable to that of the analogous Pd-catalyzed cyanation methodology.

The synthesis of phthalocyanines containing both nitrile and non-peripheral alkyl or alkoxy side-chains

The synthesis of a number of phthalocyanines containing four or eight peripheral nitrile groups in addition to eight non-peripheral alkyl or alkoxyl side-chains is described. These materials are derived from the tetracyano- and tricyano-benzene derivatives prepared by the Rosenmund von Braun reaction of 1,2,4,5-tetrabromo-3,6-didodecylbenzene or 1,2,4,5-tetrabromo-3,6-hexyloxybenzene. Attempts to polymerise 1,2,4,5-tetracyano-3,5-didodecylbenzene to form a soluble polyphthalocyanine derivative failed.

Catalytic Rosenmund–von Braun reaction in halide-based ionic liquids

Ionic liquids based on 1- n-butyl-3-methylimidazolium halide salts (bmiX) have been used as an effective reusable reaction media in the Rosenmund–von Braun reaction of aryl halides and NaCN using copper(I) salts as catalysts. Product isolation is achieved by simple extraction using organic solvents. The copper catalysts immobilized in ionic liquid media can be reused continuously.

11C]copper(I) cyanide: a new radioactive precursor for 11C-cyanation and functionalization of haloarenes

Radiosynthesis of [cyano- 11C]benzonitriles, [carboxyl- 11C]benzoic acids, [carbonyl- 11C]benzamides and [tetrazoyl- 11C]5-biphenyl-1H-tetrazoles are described. [Cyano- 11C]benzonitriles were prepared using the Rosenmund-von Braun reaction in one step from [ 11C]hydrogen cyanide via [ 11C]copper(I) cyanide in 2 min. [Carboxyl- 11C]benzoic acids and [carbonyl- 11C]benzamides were prepared from [cyano- 11C]benzonitrile-complex using basic hydrogen peroxide for 3 min in N, N-dimethylformamide at 180 and 80°C, respectively. [Tetrazoyl- 11C]5-biphenyl-1H-tetrazoles were obtained from [cyano- 11C]benzonitrile-complexes in 7 min by cyclization with trimethyltin azide followed by acid hydrolysis at 180°C. These labelled compounds were obtained in a one-pot procedure with good average specific radioactivities [500 mCi/μmol (18.5 GBq/μmol) at the end of synthesis] and in satisfactory average radiochemical yields (24–69%) at 40 min from the end of radionuclide production. This new radioactive precursor. [ 11C]copper(I) cyanide, should give access to new 11C-labelled ligands for positron emission tomography.