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The reaction of 1,1,1-trifluoro-N-phenylmethanesulfonamide with bromoacetonitrile quantitatively afforded N-(cyanomethyl)-1,1,1-trifluoro-N-phenylmethanesulfonamide which reacted with sodium azide to give the corresponding [2+3]-cycloaddition product, 1,1,1-trifluoro-N-phenyl-N-(1H-tetrazol-5-ylmethyl)­methanesulfonamide, in a moderate yield.

Trifluoromethanesulfonamide and its sodium salt reacted with bromoacetonitrile to give a mixture of N-(cyanomethyl)trifluoromethanesulfonamide and N,N-bis(cyanomethyl)trifluoromethanesulfonamide at ratios of 1:1 and 1:14, respectively.

Two series of cholestane-based diamines (1,2 and 1,3) were synthesized using simple and efficient procedures. The convenient substrates for these syntheses were cholesteryl mesylate and tosylate, which were converted to appropriate amines via easily obtained azides. The final diamines were prepared using a substitution reaction with bromoacetonitrile (in the case of 1,2-diamines) or condensation with acrylonitrile (in the case of 1,3-diamines), followed by the reduction of intermediate aminonitriles. Furthermore, the other two amines were synthesized from 16-dehydropregnenolone acetate using aza-Michael addition as a key step. Some of the diamines were subjected to complexation reactions with K2PtCl4 to form steroidal analogs of cisplatin. The synthetic methods tested in this work will allow us to prepare other cisplatin derivatives based on steroids showing anticancer properties themselves.

A practical, simple, and efficient copper-catalyzed atom transfer radical addition reaction of alkenes with α-bromoacetonitrile is realized. With this methodology, various γ-bromonitriles and β,γ-unsaturated nitriles were efficiently constructed.

The haloacetonitriles (HANs) is an emerging class of nitrogenous-disinfection byproducts (N-DBPs) present in disinfected drinking, recycled, processed wastewaters, and reuse waters. HANs were identified as primary forcing agents that accounted for DBP-associated toxicity. We evaluated the toxic characteristics of iodoacetonitrile (IAN), bromoacetonitrile (BAN), dibromoacetonitrile (DBAN), bromochloroacetonitrile (BCAN), tribromoacetonitrile (TBAN), chloroacetonitrile (CAN), dichloroacetonitrile (DCAN), trichloroacetonitrile (TCAN), bromodichloroacetonitrile (BDCAN), and chlorodibromoacetonitrile (CDBAN). This research generated the first quantitative, comparative analyses on the mammalian cell cytotoxicity, genotoxicity and thiol reactivity of these HANs. The descending rank order for HAN cytotoxicity was TBAN ≈ DBAN > BAN ≈ IAN > BCAN ≈ CDBAN > BDCAN > DCAN ≈ CAN ≈ TCAN. The rank order for genotoxicity was IAN ≈ TBAN ≈ DBAN > BAN > CDBAN ≈ BDCAN ≈ BCAN ≈ CAN ≈ TCAN ≈ DCAN. The rank order for thiol reactivity was TBAN > BDCAN ≈ CDBAN > DBAN > BCAN > BAN ≈ IAN > TCAN. These toxicity metrics were associated with membrane permeability and chemical reactivity. Based on their physiochemical parameters and toxicity metrics, we developed optimized, robust quantitative structure activity relationship (QSAR) models for cytotoxicity and for genotoxicity. These models can predict cytotoxicity and genotoxicity of novel HANs prior to analytical biological evaluation.

A green and cheap protocol for the photocatalytic atom transfer radical addition (ATRA) of bromoacetonitrile to aliphatic alkenes is presented. The use of benzoin methyl ehter as the photocatalyst and irradiation using a household lightbulb leads to a highly useful synthetic method for the conversion of a wide range of substituted aliphatic olefins into the corresponding bromonitriles.

A synthetically simple and convenient approach to tetrasubstituted thiophenes with rare combination of the alkoxy, amino, and cyano groups has been developed. The assembly of polyfunctionalized thiophene ring is implemented in one preparative step by sequential addition of isothiocyanate and 2-bromoacetonitrile to the lithiated (with n-BuLi) alkoxyallene. The reaction proceeds through in situ formation and intramolecular cyclization of cyanomethyl 2-alkoxy-N-buta-2,3-dienimidothioate (1-aza-1,3,4-triene).

A straightforward synthesis of highly functionalized pyrroles was achieved by a one-pot reaction between 3-(cyanomethyl)benzimidazolium salts and acetylenic dipolarophiles under reflux in 1,2-epoxybutane. The new pyrroles can also be obtained by a one-pot three-component reaction from substituted benzimidazoles, bromoacetonitrile, and activated acetylenes. The structures of the pyrroles were deduced by NMR spectroscopy and confirmed by X-ray crystal analysis.

A visible-light induced cyanomethylation of N-aryl acrylamides with bromoacetonitrile followed by intramolecular cyclization has been explored. This transformation exhibits a wide substrate scope and significant functional group tolerance, providing a facile synthetic approach and highly efficient access to cyanomethylated oxindoles.

2′-Hydroxyacetophenone was alkylated with a range of substituted benzyl and heteroaryl alcohols to afford the corresponding C-alkylated products in good yields under microwave irradiation. The C-alkylated products were reacted with bromoacetonitrile to afford 2-amino-3-benzyl 1,4-naphthoquinone derivatives in moderate yields.

The mechanism of cobalt-catalyzed methoxycarbonylation of bromoacetonitrile and methyl 2-halogen acetate was computationally investigated by comparing three different reaction pathways with the consideration of solvation and countercation effect. Pathway B, which goes through the addition of MeO− to (RCH2)Co(CO)4 and the elimination of [(RCH2)Co(CO)3(COOMe)]− to afford ester, is found to be the most kinetically favored. The previously proposed pathway A, which goes through twice SN2 reaction, and herein proposed pathway C, which undergoes the conventional migratory CO insertion of (RCH2)Co(CO)4 and further methanolysis of (RCH2CO)Co(CO)4 intermediate, are less favored due to their higher barrier. The thermodynamic contribution of countercation is distinct, but the mechanism preference still keeps.

A new and efficient protocol for the synthesis of aryloxyacetonitriles based on arylboronic acids with 2-bromoacetonitrile has been developed using eco-friendly hydrogen peroxide as oxidant under metal-free conditions. This method is compatible with arylboronic acid attached sensitive substituent and obtains desired product in moderate to good yield.

International audience; A series of reactions have been performed by mixing 2-diphenylphosphino-6-methyl-pyridine (dpPyMe) and [Cu(CH3CN)4]BF4 in different molar ratios. Starting from equimolar quantities of dpPyMe and Cu+, a dinuclear Cu(I) complex with two P,N binucleating bridging ligands has been obtained. This compound is stable in the solid state, however ligand exchange reactions leading to a mixture of species have been evidenced in solution. By increasing the amount of dpPyMe, the reaction of dpPyMe and [Cu(CH3CN)4]BF4 afforded the dinuclear Cu(I) complex [Cu2(μ-dpPyMe)3(CH3CN)](BF4)2 in which the three bridging dpPyMe ligands are in a head-to-head arrangement. This compound is remarkably stable in solution. It has been also shown that the axial CH3CN ligand of [Cu2(μ-dpPyMe)3(CH3CN)](BF4)2 can be suitably exchanged with other nitrile ligands [benzonitrile, 4-(dimethylamino)-benzonitrile, 4-nitrobenzonitrile and bromoacetonitrile] but also with triphenylphosphine oxide. The electrochemical and photophysical properties of the resulting complexes have been systematically investigated. The [Cu2(μ-dpPyMe)3(L)](BF4)2 derivatives are weak emitters in solution but remarkable emission quantum yields (6 to 46%) have been found in rigid matrices at room temperature. One complex was utilized as active material for preliminary tests in LEC devices.

A simple and efficient method has been developed for the synthesis of α-functionalized amide from alcohols and nitriles in the presence of silica gel supported sodium hydrogen sulfate ­(NaHSO4/SiO2). For example, benzhydrol was allowed to react with bromoacetonitrile in the presence of NaHSO4/SiO2 in 1,2-dichloroethane to yield N-(diphenylmethyl)-2-bromoacetamide.

An inexpensive one-pot green methodology has been developed for the synthesis of thiazolo[2,3- a ]isoquinolin-4-ium derivatives by the reaction of different derivatives of isoquinoline and 2-bromoacetophenone/bromoacetonitrile with benzoyl isothiocyanate in aqueous micellar medium.

A facile and efficient protocol for the visible-light-promoted radical oxycyanomethylation of olefinic amides with bromoacetonitrile has been developed, affording a series of 4-cyanoethylated benzoxazine derivatives in moderate to excellent yields. The reaction featured with diverse functional group tolerance and mild reaction conditions.

The N-alkylation of pyridines with cyanohydrin triflates or α-halonitriles furnishes 1-(1-cyanoalkyl)pyridinium salts that can react with nitroolefins under basic conditions to furnish polysubstituted indolizines. Overall, the indolizine core can be constructed from a pyridine, two aldehydes, and a nitroalkane, and no undesired functional groups remain in the products. When bromoacetonitrile was used for the N-alkylation, indolizine-3-carbonitriles were obtained instead. The pyridine component may be replaced by other azines, giving rise to related heterocyclic systems.

Base decomposition of 4-(substituted phenyl)-1,2,3-selenadiazoles at room temperature resulted in 2-(substituted phenyl)-ethynylselenolate anions, which were immediately reacted with bromoacetonitrile to give a series of 2-(substituted phenyl)ethynylselanylacetonitriles.

Zinc mediated addition reaction of bromoacetonitrile with aryl aldehydes and ketones produces β-hydroxynitriles under solvent-free conditions. The valuable feature of the methodology are solvent-free and catalyst-free conditions and short reaction times (5 min).

An efficient method for the selective "N1" alkylation of indazoles is described. Use of alpha-halo esters, lactones, ketones, amides, and bromoacetonitrile provides good to excellent yield of the desired N1 products.

Addition of carboxylic acid dianions to bromoacetonitrile lead, in good yields,to the corresponding gamma-cyanoacids, which on hydrogenation yielded gamma-amino acids. This two step methodology improves upon previously described results. Poor e.e's resultedfrom our attempts to drive the enantioselectivity of this transformation by chiral amide induction.

5‐Cyano‐1,3‐dioxoalkanes were prepared by reaction of 1,3‐dicarbonyl dianions with bromoacetonitrile.

One‐pot Wittig reactions of ethyl bromoacetate and bromoacetonitrile with aldehydes in the presence of PPh3 and LiOH in water were investigated. Most of the olefination reactions completed within 5–120 min in refluxing water containing 1.2 M LiCl to afford the olefin products in 71–97% yields with 100:0–55:45 ratios of E:Z isomers.

N-Acridin-9-yl methyl N′-acridin-9-yl thiourea spontaneously spiro cyclises via nucleophilic attack of the methylene carbon onto the C-9 of the other acridine moiety. The thiourea, upon reaction with bromoacetonitrile, provided a spiro fused-bicyclic product displaying unusual dynamic behavior.

2-Deoxy-4,5:6,7-di-O-isopropylidene-β-D-manno-oct-4-ulo-4,8-pyranosononitrile (3) and 2-deoxy-4,5:6,8-di-O-isopropylidene-α-L-gulo-oct-4-ulo-4,7-furanosononitrile (5) were prepared by a high stereocontrolled indium-mediated Reformatsky-type reaction of 2,3:4,5-di-O-isopropylidene-β-D-arabino-hexos-2-ulopyranose (1) and 2,3:4,6-di-O-isopropylidene-α-L-xylo-hexos-2-ulofuranose (2) with bromoacetonitrile, repectively. The configurations at C(3) in 3 and 5 were established by chemical correlation.

An inexpensive one-pot green methodology has been developed for the synthesis of thiazolo[2,3- a ]isoquinolin-4-ium derivatives by the reaction of different derivatives of isoquinoline and 2-bromoacetophenone/bromoacetonitrile with benzoyl isothiocyanate in aqueous micellar medium.

Zinc mediated addition reaction of bromoacetonitrile with aryl aldehydes and ketones produces β-hydroxynitriles under solvent-free conditions. The valuable feature of the methodology are solvent-fr...

A series of aryldiazonium tetrafluorborates dissolved in nitriles have been converted into the corresponding anilides in almost quantitative yield in 1 min by microwave irradiation. When bromoacetonitrile was used, 2,4-bis(bromophenyl)-quinazoline was formed. The reaction of malononitrile with the diazonium salt, in DMF as a solvent, afforded 2-(dimethylaminomethylene) malononitrile and phenylhydrazone propanedinitrile.

The addition of dianions of carboxylic acids to bromoacetonitrile, leads, in good yields, to the corresponding γ-cyanoacids that give γ-aminoacids on hydrogenation. This two-step methodology improves the results previously described.

A convenient method has been devised for the preparation of the spirodihydro-acridinethiazolines 5a-j by the treatment of thioureas 3a-e with methyl bromoacetate and bromoacetonitrile via non-isolable isothioureas 4a-j and their subsequent cyclization with methanolic sodium methoxide.

Six novel, asymmetric, 19- to 26-membered polyazadipyridinocyclophane scaffolds 1–6 have been synthesized in high yields by an efficient cyclization of ditosylate 39 with the appropriate six fully protected triamines 40–45 , followed by removing the 2-nitrobenzenesulfonyl protecting groups. Intermediate 39 was synthesized by the Mitsunobu reaction of 2-nitrobenzenesulfonamide ( 37 ) with 2,6-pyridinedimethanol ( 36 ), and a subsequent tosylation of the resulted diol 38 . The fully protected asymmetric triamines 41 and 43 were prepared from the corresponding commercially available triamines 52 and 53 . A new synthetic route was developed for the synthesis of the protected asymmetric triamines 44 and 45 . All reactions were carried out at room temperature in high yields. The reaction of t -Boc-protected scaffold 1 , having three reactive sites, with nine benzylic bromides and bromoacetonitrile, using a solution phase simultaneous addition of functionalities combinatorial strategy, gave t -Boc-protected library 7 containing 1000 compounds. Deprotection of library 7 generated the intermediate library 8 with one reactive site. Subsequent reactions at the unsubstituted position of 8 with various functionalities by four types of reactions gave sixteen final libraries 9–24 . Libraries 7–24 have different functionalities at the fixed position, and each of them contains 1000 compounds. The reaction of scaffold 2 , having four reactive sites without protecting groups, with six sets of polar functionalities afforded eleven diverse libraries 25–35 containing 625 compounds in each library. Totally, twenty-nine libraries containing 24875 compounds were obtained. Eight libraries exhibited antibacterial activity against Escherichia coli imp − and Streptococcus pyogenes with the MIC's of 2 to 10–50 μM. Seven libraries disrupted HIV-1 tat/TAR protein-RNA interactions with IC 50 's as low as 0.08 μM.

In the presence of tin powder, the addition of bromoacetonitrile to aldimines gives β-amino nitriles in THF. Chlorotrimethylsilane can accelerate the reaction.

Mono or di-protected aldoses react with methyl bromoacetate or bromoacetonitrile, in presence of tri-n-butylphosphine and zinc, to give stereoselectively with good yields the corresponding E unsaturated Wittig adducts.

Iodoacetonitrile and bromoacetonitrile were used to enhance the sensitivity of chromatographically difficult compounds. Selective derivatization occurs with acidic hydroxyl, amino, and amide functional groups but does not occur for the alcohotic hydroxyl group. Numerous examples of model compounds (e.g., phenols, organic acids, fatty acids, nonsteroidal antiinflammatory drugs, and xanthines) are given. The use of an element-specific detector for nitrogen-containing compounds is described, and some electron impact GC/MS data are provided for the derivatized model compounds

The organoindium reagent, derived from indium metal and bromoacetonitrile, reacted with carbonyl compounds in the presence of chlorotrimethylsilane to give, after hydrolysis, β-hydroxy nitriles. The coupling proceeded with high chemoselectivity, though the diastereoselectivity was low.

(±)-Lamprolobine 1 and (±)-epilamprolobine 4 were prepared by a route featuring sulphide contraction of thiolactam 7 with bromoacetonitrile to give vinylogous cyanamide 8 , reduction and ring closure to the unsaturated quinolizidine 11 , and selective reduction of the latter to set up appropriate stereochemistry for the target alkaloids.

The organoindium reagent, derived from indium metal and bromoacetonitrile, reacted with carbonyl compounds in the presence of chlorotrimethylsilane to give, after hydrolysis, β-hydroxy nitriles. The coupling proceeded with high chemoselectivity, though the diastereoselectivity was low.

Cyanomethylation by bromoacetonitrile of sodium or lithium enolates derived from (4S,5R)-3-acyl-4-methyl-5-phenyl-1,3-oxazolidin-2-ones usually shows good stereoselectivity; although the reaction of 3-(3-carboxypropanoyl)oxazolidinone 5d is exceptionally unselective, the 3-(pent-4-enoyl)- and 3-(3,4-dimethoxyhydrocinnamoyl)oxazolidinones 5e and 5f are found to be effective synthetic equivalents of 5d. The cyanomethylation products can be converted into 2-substituted derivatives of 4-aminobutanoic acid (γ-aminobutyric acid, GABA) by the alkaline hydrolysis of the oxazolidinone chiral auxiliary followed by hydrogenation of the cyano group.