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Review: recent breakthroughs in SN2-type nucleophilic fluorination reactions using alkali metal fluorides promoted by protic solvents; 50 refs.

Investigation of a suitable access to the cyclization precursors (III) and (VII) shows that EDC·HCl is an optimal agent which allows the isolation of the pure products by simple filtration.

A highly efficient promoter for the SN2 reaction of various substrates by enhancing the reactivity of alkali metal salts is presented.

The novel method is based on the metal-free intramolecular nucleophilic ring closing of diaryliodonium salts such as (I).

A convenient and mild in situ two-step method for the synthesis of the title compounds is reported from easily preparable starting materials.

The title mixtures are employed to chlorinate activated arenes and the α-position of ketones.

Polymer-supported pentaethylene glycols (PSpentaEG) as promising catalysts for nucleophilic fluorination with alkali metal fluoride (MF) could significantly enhance the nucleophilicity of MF and provide simple purification and recycling in the reaction. Furthermore, by their synergistic effect, the combination of PSpentaEG and a tert-alcohol media system showed tremendous efficiency in the fluorination of base-sensitive substrates such as sec-alkyl halide.

A general procedure for the high throughput synthesis of 1,4-disubstituted 1,2,3-triazoles under optimized reaction conditions without conventional purification is developed.

Copper nitride nanoparticles supported on a mesoporous superparamagnetic silica microsphere exhibit superior catalytic activity toward the Huisgen cycloaddition of azides and alkynes (15 examples).

We have synthesized several bicyclic heteroaromatic compounds with bridgehead nitrogen from N-amine salts of heteroaromatic amines. 2-Amino and 2-unsubstituted thiazolo[3,2-b][l,2,4]triazole derivatives 2a-b were prepared by the cyclization reaction from N-amine salts of aminothiazole-5-yl(N-methoxyimino)acetate with cyanogen bromide and formamidine acetic acid salt, respectively. 2-Methylthiazolo[3,2-b][1,2,4]triazole 2c was obtained from N-acetylated N-amine salt of aminothiazole-5-yl(N-methoxyimino)acetate by the cyclization reaction in the presence of polyphosphoric acid (PPA). 2-Substituted and 2-unsubstituted thiazole[3,2-b][1,2,4]triazole derivatives 2a-c were coupled with 7-aminocephalosporanic acid (7-ACA). Coupled cephalosporin derivatives 1a-c did not have good antibacterial activities in vitro.

Binaphthol-derived chiral ketones 1a-c were synthesized and were shown to serve as active catalysts for asymmetric epoxidation of olefins using Oxone, although their enantioselectivities were not high. However, very interestingly, the stereochemical outcome of the resulting epoxides implicates that in the epoxidation using 1a-c, the planar transition state may be more favorable than the spiro transition state.

Palladium-catalyzed functionalization at the 2-position of various 5- and 7-azaindoles was performed by Suzuki, Heck, and Stille reactions. The 2-substituted azaindoles were obtained with 5% Pd(OAc) 2 , LiCl, and KOAc in DMF at 110°C with moderate to high yields.

/NaBr reagent in organic synthesis, we have found that thisreagent facilitates the bromodecarboxylation of arylpropiolicacids very efficiently under the similar conditions. We reportherein a facile and bench-frienldy method for the bromo-decarboxylation of propiolic acids containing phenyl orthienyl groups with Oxone

A novel synthetic method using an ionic liquid (IL) for a six-membered ring-closure cyclization is described. The ring-closure cyclization by nucleophilic C-alkylation was achieved with various halo- and alkanesulfonyloxyalkyl aromatic compounds in high yields with minimal byproducts using ILs as the reaction media in the absence of any catalyst. For example, the cyclization of 2-(3-methanesulfonyloxy-propoxy)naphthalene (1a) to 2,3-dihydro-1H-naphtho[2,1-b]pyran (2) in IL [bmim][PF6] proceeded selectively at 150 °C for 24 h in 85% yield.

Encouraged by a synergistic effect on nucleophilic fluorination, an imidazolium mesylate salt ( 1a ) possessing two different solvent properties in one molecule— tert -alcohol and ionic liquid was utilized in various nucleophilic substitution reactions. By a comparison study with 1- n -butyl-3-methylimidazolium ionic liquids, 1a has proved to be a better phase transfer catalyst even under room temperature conditions. It was successfully applied to other nucleophilic substitution reactions such as fluorination, chlorination, bromination, iodination, acetoxylation, azidation, and cyanation.

Seventeen tetrahydroisoquinoline derivatives were designed, synthesized and evaluated for inhibition of NO production in lipopolysaccharide-stimulated BV-2 microglial cells. Compounds 5a, 9c and 11a potently attenuated NO production by >60%, and 5a and 11a inhibited BH4 production by >48% at 100 μM. In particular, N-ethylcarbonyl-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline (11a) reduced NO production by 64% and tetrahydrobiopterin (BH4) production by 49%. Introducing longer alkyl component at C1 or N2 position led to attenuation of the inhibitory effect. It is possible that 11a inhibits NO production by blocking BH4-dependent dimerization of newly synthesized iNOS monomers.

A highly efficient method was developed for nucleophilic fluorination using an alkali metal fluoride through the synergistic effect of the polymer-supported ionic liquid (PSIL) as a catalyst and tert -alcohol as an alternative reaction media. This PSIL/ tert -alcohol system not only enhances the reactivity of alkali metal fluorides and reduces the formation of by-products but also allows the use of a polymer-supported catalyst protocol. As an example, the nucleophilic fluorinations of the model compound, 2-(3-bromopropoxy)naphthalene, with CsF using only tert -amyl alcohol as solvent (for 2 h reaction time), 0.5 equiv of PS[hmim][BF 4 ] in CH 3 CN (for 12 h reaction time), and 0.5 equiv of PS[hmim][BF 4 ] in tert -amyl alcohol (which is a PSIL/ tert -alcohol system for the synergistic effect; for 2 h reaction time) provided 18, 40, and 84% yield, respectively. The characteristics of the nucleophilic fluorination reactions of some halo- and alkanesulfonyloxyalkane systems to the corresponding fluoroalkanes using various alkali metal fluorides are also reported.

The fluorination of aryl triazenes can be affected by their thermal decomposition in acidic medium in the presence of fluoride ion. Typically, HF is generated in this conversion by the reaction a fluoride salt with an acid. As acid is required to decompose the aryl triazene, a major byproduct is typically the arene substituted with the counterion of acid used. Higher yields of the fluoride product can be obtained when greater amounts of the fluoride source are added, but substantial yields of the non-fluorinated byproduct are typically also produced. 16 To avoid competitive formation of the byproduct, decomposition of aryl diazosulfide using silver fluoride was attempted. 18

[reaction: see text] A novel ionic liquid methodology for pyrrole C-alkylation is described. The pyrrole alkylation is achieved with various simple alkyl halides and mesylates selectively at C2 and C5 positions in good yields with minimal byproducts under relatively mild conditions in various ionic liquids. 2-(3-Phenylpropyl)pyrrole (2a) was synthesized from pyrrole and 1-bromo-3-phenylpropane in a mixture solvent system, [bmim][SbF6] and CH3CN, in 81% yield at 115 degrees C for 44 h with 5% yield of dialkylated compound 3a.

We have designed a new family of radioligands, 3-(amino- and hydroxymethyl)-4-(5-iodopyridin-2ylthio)indoles, combining characteristically distinct moieties proven to impart successful binding ability in a variety of structurally diverse selective serotonin reuptake inhibitors recently published. Described in this article are the syntheses of 3-substituted 4-(5-iodopyrid in-2-ylthio)-indoles, featur ing successful adaptation of the modified Leimgruber-Batcho indole synthesis onto the key intermediate 1-(5-iodopyridin-2-ylthio)-2methyl-3-nitrobenzene (6) prepared from the nucleophilic aromatic substitution of chloropyridine 7 with thiophenol 8.

Nine new resveratrol derivatives, having bromo, iodo, and fluoroethyl groups, were designed and synthesized. All compounds having free phenol groups showed good free radical scavenging activity. Among them, 2-bromoresveratrol 19 has a similar free radical scavenging activity to (+)-catechin.

[reaction: see text] We have found a new synthetic method for the preparation of the alpha-bromoketones that are brominated in the less activated terminal position of unsymmetrical ketones. Brominations in short reaction times (kinetically controlled) provided internally brominated compounds as a major product. However, brominations in longer reaction times (thermodynamically controlled) gave more of the terminally brominated compound through the reversible reaction by Br(2) and produced hydrogen bromide. Several brominated compounds at the terminal position were successfully prepared through the new synthetic route.

In Os-catalysed asymmetric dihydroxylation using NMO as a co-oxidant, the combination of an ionic liquid and the new bis-cinchona alkaloid 2 generated in situ from (QN)2PHAL during reaction provided a simple and practical approach to the recycling of both catalytic components (osmium tetraoxide and chiral ligand).

2-Vinyl- or heteroaryl-substituted anilines were reacted with diphosgene in acetonitrile solution via a reactive imidoyl moiety to afford the corresponding 2-chloroquinolines. Facile syntheses of nine 2-chloroquinoline derivatives from several anilines and their postulate mechanism is described. The postulate mechanism of 2-chloroquinoline formation via imidoyl moiety as a good leaving group shows that the reaction consists of the following three steps: (1) generation of phenylisocyanate, (2) quinoline ring formation, and (3) chlorination on C2 position of quinoline.

We have found the new nucleophilic fluorination reaction of some halo- and mesylalkanes to the corresponding fluoroalkanes with KF in the presence of [bmim][BF4] under various reaction conditions. 2-(3-Methanesulfonyloxypropoxy)naphthalene (1) was used as a model compound to optimize this fluorination reaction. Whereas the fluorination of the mesylate 1 with KF in an organic solvent such as CH3CN at 100 degrees C occurred hardly even after 24 h, the same reaction in ionic liquids, [bmim][BF4], as a reaction solvent was completed within 1.5 h, affording the wanted product 2-(3-fluoropropoxy)naphthalene 2a (85%) together with the alkene byproduct 2c (10%). Very interestingly, however, the addition of water (5 equiv) completely eliminated the formation of the undesired alkene 2c and thus gave higher yield of 2a (92%, entry 2). The use of acetonitrile as a cosolvent did not affect the reactivity of the fluorination. The presence of a proper amount of cosolvent was rather desirable (94% yield of 2a). We performed fluorination reactions with other ionic liquids ([bmim][PF6], [bmim][SbF6], [bmim][OTf], and [bmim][N(Tf)2], and two other cosolvents, to find the optimal ionic liquid and cosolvent. Nine different compounds were examined, including the 10 g-synthesis of 2-(fluoromethyl)naphthalene in 93% of isolated yield.

[figure: see text] Fused 1,4-dimethoxybenzenes could be oxidized to benzoquinones by either direct oxidation or demethylation-oxidation. The oxidative demethylation of 5,8-dimethoxy-2-methylquinoline using 1.1 equiv of NBS in aqueous THF and a catalytic amount of H2SO4 at 20 degrees C for 5 min gave 2-methylquinoline-5,8-dione in 98% yield without bromination. Moreover, we can control either bromination or oxidative demethylation, or both reactions.

The regioselectivity in the reaction of 6,7-dihaloquinoline-5,8-diones with amine nucleophiles was described. In this reaction the solvent played an important role.

6-Nitroquipazine has been known as one of the most potent and selective inhibitors of serotonin transporter in vitro and in vivo. Nine derivatives of 6-nitroquipazine were synthesized and tested for their potential abilities to displace [3H]citalopram binding to the rat cortical membranes.

The new cephalosporins having N-linked quarternary ammonium salt at C-3 position were prepared from the reaction of 2-methylimino-3-methyl-1,3-thiazoline derivatives with cephalosporins. Also antimicrobial activities of those compounds were determined.

Cette reaction est appliquee a l'halogenoalkylation de la spiperone et de la N-phenylpiperazine