Selective α-bromination of aryl carbonyl compounds: prospects and challenges

The α-bromination of carbonyl compounds is one of the most important transformations and also important precursors in synthetic organic chemistry. Particularly, the side chain monobromination of carbonyl compounds has been a challenging task, because during the reaction a small amount of disubstituted or ring brominated products as an impurity is always accompanied with monosubstituted product in the reaction mixture. In recent years substantial advances have been made for the synthesis of brominated aromatic carbonyl compounds with high selectivity. In this review, we have summarized various methods for the synthesis of α-bromo aromatic carbonyl compounds.     

Bromination by means of sodium monobromoisocyanurate (SMBI)

A variety of aromatic compounds with both activating and deactivating substituents were brominated with sodium monobromoisocyanurate (SMBI) 1, diethyl ether, diethyl ether-methanesulfonic acid, trifluoroacetic acid, or sulfuric acid were employed as solvents. Thus nitrobenzene was conveniently brominated in sulfuric acid, benzene was readily monobrominated in diethyl ether-methanesulfonic acid, and phenol was selectively brominated at the ortho position under mild conditions in refluxing diethyl ether. With substituents that are easily protonated, trifluoroacetic acid may be employed as solvent in the reaction with 1, in contrast NBS was ineffective in trifluoroacetic acid. This renders 1 a superior reagent relative to NBS. In addition to aromatics, alkenes, ketones and esters were also brominated with 1. Diethyl malonate was brominated with 1 and then subjected to a Bingel reaction with NaH to afford the desired methanofullerene in reasonable yield.     

Bromine formation in solid NaBr/KNO<Subscript>3</Subscript> mixture and assay of this reaction via bromination of activated aromatics

Bromine formation in the mixture of solid NaBr and KNO₃ was observed and the process was studied in different acidified organic solvent–water mixtures by monitoring the bromination of acetanilide and other compounds, containing activated aromatic substituents. This assay is based on fast bromination reaction of these aromatic compounds, as differently from the assay of Br₂, the brominated aromatics can be easily determined by conventional gas chromatography–mass spectrometry (GC–MS) methods. It was found that bromine was generated autocatalytically on the surface of salt crystals and the reaction was characterized by a lag period, the duration of which depended on reaction conditions, and importantly on the type of the organic solvent in the reaction mixture. As the bromine formation could be easily controlled by reaction conditions, it was suggested that the studied reaction might have practical applications as an environmentally friendly and economically feasible bromination method. It was also shown that the bromination of aromatics followed the mechanism of classical electrophilic aromatic substitution reaction.     

Ultrasonically activated reduction of substituted nitrobenzenes to corresponding N-arylhydroxylamines

Arylhydroxylamines can be obtained by reduction of the corresponding nitroaromatic compounds. We report here an efficient preparation of arylhydroxylamines by a controlled reduction of nitro compounds using zinc metal and ammonium chloride under ultrasonic activation in very short reaction times.     

Silane modification and characterization of activated carbon

Activated carbons have been wildly used as adsorbents for various purpose. When used in a cigarette filter activated carbon can selectively remove a number of the vapor phase compounds to varying degrees of efficiency. To improve the wet-feeling of cigarette smoke with AC in the filter, a new method is developed to chemically functionalize a coal-based activated carbon (AC) based on silanization reaction. Silanization using 3-glycidoxypropyltrimethoxy silane was performed after the oxidized AC was reduced by lithium aluminum hydride.     

Action du n-butyllithium sur les bromo-3 halogeno-2 pyridines fluoree,chloree et bromee : Principe et etude d'une possibilite reactionnelle nouvelle : l'homotransmetallation

Apart from the common bromine-lithium exchange reaction in brominated aromatic compounds, it is possible to obtain a lithio-derivative quite different from the one usually described in such a reaction. This new reaction, which results from a special experimental conditions is called ·homotransmetalation”, and it occurs when using n-butyllithium and 3-bromo 2-halogenopyridines (1). Different behaviour is observed with the three similar compounds (1: X = F,Cl,Br). Explanations are proposed of these results. It is then possible to compare the relative stabilities of the proposed lithio-structures. It is evident that nucleophilic substitution of bromine in position 4 of the pyridine ring is easier than is usually recognised.     

Syntheses and surprising regioselectivity of 5- and 6-substituted decaboranyl ethers via the nucleophilic attack of alcohols on 6- and 5-halodecaboranes

The selective syntheses of new classes of decaboranyl ethers containing a range of functional groups substituted at the B5 or B6 positions were achieved through the reaction of alcohols with halodecaboranes. The surprising regioselectivity of the reaction, where the reaction of the 6-halodecaboranes (6-X-B(10)H(13)) with alcohols yielded the 5-substituted decaboranyl ethers (5-RO-B(10)H(13)) and the reaction with 5-halodecaboranes (5-X-B(10)H(13)) gave the 6-substituted decaboranyl ethers (6-RO-B(10)H(13)), was confirmed by NMR and X-ray crystallographic analyses. The crystallographic determinations also showed that the decaboranyl ethers had shortened B-O bonds and apparent sp(2) hybridization at oxygen indicating significant π-backbonding from oxygen to the cage boron. A possible substitution mechanism was computationally identified involving: (1) initial nucleophilic attack by the alcohol-oxygen at a site adjacent to the 5- or 6-halo-substituted boron, (2) movement of the terminal hydrogen at the point of attack to a bridging position, (3) formation of a 5-membered (B-O-H-Cl-B) cyclic transition state allowing the acidic methanolic-hydrogen to bond to the halogen, (4) release of HX, and finally (5) movement of a bridging hydrogen into the vacated terminal position. Deuterium labeling studies confirmed the movement of hydrogen from a bridging position of the halodecaborane into the halogen-vacated terminal position on the decaboranyl ether product. The relative reaction rates of the 6-X-B(10)H(13) compounds (X = F, Cl, Br, I) with alcohols were likewise found to be consistent with this mechanism.     

Controlled pyrolysis of polyethylene/polypropylene/polystyrene mixed plastics with high impact polystyrene containing flame retardant: Effect of decabromo diphenylethane (DDE)

The pyrolysis of polyethylene(PE)/polypropylene(PP)/polystyrene(PS) mixed with high impact polystyrene (HIPS-Br) containing decabromo diphenylethane (DDE) as a brominated flame retardant with antimony trioxide as a synergist was performed under controlled temperature programmed pyrolysis (two steps) conditions to understand the decomposition behaviour and evolution of brominated hydrocarbons from flame-retardant additives. The liquid products were extensively analyzed by gas chromatographs equipped with FID, ECD, MSD, TCD, AED and FT-IR. The solid residue samples were analyzed by powder X-ray diffraction and combustion followed by ion-chromatography. The controlled pyrolysis of PE/PP/PS/HIPS-Br significantly affected the decomposition behaviour of HIPS-Br and subsequently the formation of decomposition products. GC/ECD analysis confirmed that the brominated hydrocarbons were concentrated in step 1 liquid products leaving less brominated hydrocarbons in the step 2 liquid products, similar to the decabromo diphenyl ether flame retardant containing mixed plastics. The yield of liquid products in step 1 from 3P/DDE-Sb(5) was 5 wt% and from 3P/DDE-Sb(0) was 2.4 wt%. The presence of antimony in the DDE containing plastics affected the yield of liquid, gas and residue products. ECD analysis showed that the presence of antimony increased the Br containing hydrocarbons and step 1 has 3-4 times higher brominated compounds than step 2 hydrocarbons in both the samples.     

The substrate specificity of a glucoamylase with steroidal saponin-rhamnosidase activity from Curvularia lunata

In previous work, we studied and reported that an enzyme from Curvularia lunata 3.4381 had the novel specificity to hydrolyze the terminal rhamnosyl at C-3 position of steroidal saponin and obtained four transformed products; the enzyme was purified and ascertained as glucoamylase (EC 3.2.1.3 GA). In this work, the enzyme exhibiting steroidal saponin-rhamnosidase activity was systematically studied on 21 steroidal saponins and 6 ginsenosides. The results showed that the α-1,2-linked end-rhamnosyl residues at C-3 position of steroidal saponins could be hydrolyzed to corresponding secondary steroidal saponins, among which 18 compounds were isolated and identified, including 3 new secondary compounds. For the furostanosides having glucosyl residues at the C-26 position, hydrolysis occurred first at end-rhamnosyl at C-3 position to produce secondary furostanosides. The reaction of hydrolyzing glucosyl at C-26 position depended considerably on longer reaction times yielding the corresponding secondary spirostanosides (without rhamnosyl and glucosyl residues). The enzyme had the strict specificity for the terminal α-1,2-linked rhamnosyl residues of linear chain, or the terminal α-1,2-linked rhamnosyl residues with branched chain of 1,4-linked glycosyl residues of sugar chain at C-3 position of steroidal saponins, it was not specific for different aglycones, different glycons, and the number of glycon of sugar chain of steroidal saponin. The end-rhamnosyl of ginsenosides and p-nitrophenyl-α-l-rhamnopyranoside (pNPR) could not be hydrolyzed by the enzyme from C. lunata.     

Synthesis of multiply substituted, ion channel forming octi(p-phenylene)s: theme and variations

[reaction: see text] To facilitate the access to unique models for biological processes, we examined six different synthetic routes to octi(p-phenylene) rods with lateral and terminal substituents R(L) and R(T). This systematic study allowed us to increase to overall yield for the synthesis of a new class of oligo(p-phenylene) ionophores about 20 times and to provide general insights into the practicability of synthetic routes to multiply substituted molecular rods.     

Tandem chalcone-sulfonamide hybridization,cyclization and further Claisen–Schmidt condensation: Tuning molecular diversity through reaction time and order and catalyst

We here report the synthesis of novel chalcone-sulfonamide compounds based on the hybridization at 2′ position and nitro substitution at the side chalcone phenyl ring followed by tandem cyclization into quinolinone derivatives and then a further aldol condensation only as a function of the reaction time. Therefore, for the first time, we have controlled the sequential preparation of chalcone-sulfonamide hybrids, quinolinones and then (E)-3-ene-2,3-dihydroquinolinones simply stopping reaction over increasing time periods. Furthermore, a new molecular scaffold based on a chalcone-(bis)sulfonamide hybrid has been gotten through changing the sequence of coupling reactions and catalyst. This study means practical and useful ways of constructing in high yields new biologically active compounds bearing diversified molecular scaffolds.     

Bromination of quinoxaline and derivatives: Effective synthesis of some new brominated quinoxalines

The synthesis of brominated quinoxaline derivatives starting from several kinds of quinoxaline by different bromination strategies was studied. First the synthesis of some brominated quinoxalines was accomplished along with the development of an alternative and effective synthesis of some known compounds. A new, clean, and effective synthetic method for selective reduction of quinoxaline to 1,2,3,4-tetrahydroquinoxaline was also developed. The products obtained were characterized by means of NMR spectroscopy, elemental analyses, and mass spectrometry.     

Use of an efficient polystyrene‐supported cerium catalyst for one‐pot multicomponent synthesis of spiro‐piperidine derivatives and click reactions in green solvent

One‐pot multicomponent reactions are very demanding in synthetic organic chemistry. Here we report a new polystyrene‐supported cerium catalyst (PS‐Ce‐amtp) obtained via an easy two‐step procedure, which was thoroughly characterized using various techniques. PS‐Ce‐amtp catalyses the environmentally benign one‐pot multicomponent synthesis of spiro‐piperidine derivatives through the reaction of substituted aniline, cyclic active methylene compound and formaldehyde at room temperature. The catalyst also exhibits excellent catalytic activity in one‐pot synthesis of 1,4‐disubstituted 1,2,3‐triazoles via click reaction between in situ generated azides (derived from anilines and amines) and terminal alkynes. The catalyst can be recovered easily after reaction and reused five times without significant loss in its catalytic activity. The advantageous features of this catalyst are atom economy, operational simplicity, short reaction times, easy handling and high recycling efficiency.     

Postsynthetic Exterior Decoration of an Organic Cage by Copper(I)‐Catalysed A3‐Coupling and Detection of Nitroaromatics

A new synthetic protocol based on one‐pot, copper(I)‐catalysed multicomponent reaction of formaldehyde, secondary amine and terminal alkyne has been employed to postsynthetically modify a self‐assembled nanoscopic organic cage. By employing this synthetic strategy, three new cages appended with phenyl‐, xylyl‐ and naphthyl‐acetylene moieties have been synthesised. The resulting modified cages were characterised by using a range of spectroscopic techniques. The synthesised cages were fluorescent and thus one of them was tested to explore the potential use of such compounds as chemosensors for the detection of nitroaromatics. Experimental findings suggest a high selective quenching of initial fluorescence intensity in the presence of nitroaromatic compounds. Furthermore, it has been observed that among the various nitroaromatics tested, nitrophenolic compounds have better quenching ability.     

Facile Oxime Ether Synthesis: Free Carbonyl Compound Derivatization by a Brominated O-Benzylhydroxylamine

The lipid peroxidation of fatty acids leads to secondary products, among which several carbonyl compounds are of concern in food toxicology. The detection of these reactive aldehydes for identification and evaluation is required. Derivatization is necessary to improve their stability and detection in liquid chromatography/high-resolution mass spectrometry (LC/HRMS) trace analyses. Therefore, a brominated O-benzylhydroxylamine, namely 1-((ammoniooxy)methyl)-2-bromobenzene chloride, was selected as a new probe for the mild and selective derivatization of carbonyl compounds. New oxime ethers were thus synthesized under mild reaction and workup conditions, with full analytical characterization. The relevance of the chemical reaction was assessed with nine aldehydes, especially conjugated and deuterium-labeled aldehydes, and two ketones. Virtually, the reaction should be applicable to a large set of carbonyl compounds for derivatization in complex biological samples and selective detection of the in situ–synthesized brominated oxime ethers by LC/HRMS methodology.     

An efficient synthesis of brominated 4-alkyl-2(5H)-furanones

A versatile method for the synthesis of novel brominated 4-alkyl-2(5H)-furanones under mild reaction conditions is described. This synthetic strategy requires only one chromatographic separation over six steps and employs the cyclodehydration of brominated levulinic acid as the key transformation.     

Electrophilic Bromination of Alkenes,Alkynes, and Aromatic Amines with Iodic Acid/Potassium Bromide Under Mild Conditions

Bromination of alkenes, alkynes, and aromatic amines has efficiently been carried out at room temperature in short reaction times using HIO₃/KBr in CH₂Cl₂/H₂O (1:1) to prepare corresponding brominated compounds in excellent yields.     

Gas chromatography and mass spectrometry of methoxylated polybrominated diphenyl ethers (MeO-PBDEs)

Twenty-six methoxylated polybrominated diphenyl ethers (MeO-PBDEs) were characterized by gas chromatography (GC) on four different GC columns with different lengths and polarities, as well as by mass spectrometry using three ionization techniques, electron ionization (EI), electron capture negative ionization (ECNI) and positive ion chemical ionization (PICI). MeO-PBDE congeners with similar retention times on a nonpolar GC column were separated when analyzed on a polar GC column. EI can be used to determine the position of the methoxy substituent (ortho, meta or para) relative to the diphenyl ether oxygen in the MeO-PBDEs. The PICI ionization technique is shown to be valuable to generate structural information of the MeO-PBDEs, i.e. the degree of bromination on both the methoxy-substituted ring and the entirely brominated phenyl ring can be obtained. This structure information can also be achieved for certain MeO-PBDEs with the methoxy group in ortho position to the diphenyl ether bond in ECNI mode. Like other brominated compounds ECNI is preferable when analyzing environmental samples for quantification of MeO-PBDEs because of the formation of bromide ions, which enables low detection limits.     

含富勒烯结构单元酞菁的研究概况

通过不同的合成方法,将富勒烯嫁接到酞菁环的周边或轴向位置上,可以形成一类新型的具有特殊结构和性质的酞菁一富勒烯化合物.综述了具有代表性的含富勒烯结构单元的酞菁的合成及电化学、光致电子转移、分子聚集和自组装等方面的研究概况.     

A new, iterative strategy for the synthesis of unsymmetrical polyynes: application to the total synthesis of 15,16-dihydrominquartynoic acid

[reaction: see text] A new iterative strategy for the synthesis of unsymmetrically substituted polyynes has been developed. The starting bromoalkyne is homologated by one acetylene unit through palladium-catalyzed cross-coupling with a TIPS-protected terminal acetylene and a subsequent in situ one-pot AgF-mediated desilylative bromination. The utility of this new synthetic method is demonstrated by its application to the total synthesis of (S)-(E)-15,16-dihydrominquartynoic acid.