Isoprene-catalysed lithiation: deprotection and functionalisation of imidazole derivatives

The isoprene-catalysed lithiation of different 1-substituted imidazoles (1) (such as trityl, allyl, benzyl, vinyl, N,N-dimethylsulfamoyl, para-toluenesulfonyl, tert-butoxycarbonyl, acetyl, trimethylsilyl, tert-butyldimethylsilyl derivatives) leads to the cleavage of the protecting group producing 1H-imidazole. The use of 1-(diethoxymethyl)imidazole (3) in the same lithiation reaction allows the preparation of the corresponding 2-lithio intermediate, which by reacting with different electrophiles leads to 2-functionalised imidazoles 4.     

Stereoselective functionalization of 2-(1-aminoalkyl)aziridines via lithiation of aziridine-borane complexes

Highly selective functionalization of the aziridine ring of (2S,1'S)-2-(1'-aminoalkyl)aziridines 1, through successive formation of aziridine-borane complexes, lithiation, treatment with a variety of electrophiles and final decomplexation is described. The influence of the structure of the starting complexes 2 and of the electrophiles in the stereoselectivity of this process has been studied. Finally, successive double lithiation-electrophile reactions were carried out affording enantiopure 1,2,3,3-tetrasubstituted aziridine-borane complexes with high selectivity.     

Regioselective lithiation of benzyl imidazole: Synthesis and evaluation of new organocatalysts for trans-diol functionalization.

Abstract

Benzyl imidazole was successfully lithiated using n-BuLi at ?78?°C and verified by deuterium incorporation. The chemical reaction of the lithiated benzimidazole was explored with a series of different electrophiles. This approach was utilized to synthesize new anti and syn diphenyl organocatalysts for trans-diol functionalization.     

Syntheses and structures of new luminescent B(III) complexes: BPh2(2-(2-pyridyl)naphtho[b]imidazole) and BF2(2-(2-pyridyl)naphtho[b]imidazole)

A novel chelating ligand, 2-(2-pyridyl)naphtho[b]imidazole (PNI) has been synthesized and structurally characterized. The PNI molecule reacts readily with BPh₃ and BF₃ to form BPh₂(2-(2-pyridyl)naphtho[b]imidazole) (1) and BF₂(2-(2-pyridyl)naphtho[b]imidazole) (2), respectively. The structures of PNI and 1 were determined by single crystal X-ray diffraction, while that 2 by spectroscopic methods. The structure of 1 reveals that the boron center is four-coordinated. The electroluminescent device using 1 as the emitting layer shows bright yellow luminescence with a maximum emission peak at 540 nm. Complexes 1 and 2 form a new family of organometallic emitting materials which could be of interest for practical applications.     

Synthesis and Structures of the Ligands 1‐Methylimidazol‐2‐yl(pyridin‐2‐yl)methanone {(py)(mim)CO} and 1‐Benzylimidazol‐2‐yl(1‐phenylaldimine) (PhN=CHbim) as their Tetracarbonylmolybdenum(0) Complexes [Mo(CO)4(L2‐N,N′)]

The complexes [Mo(CO)₄(L₂‐N,N′)] [L₂ = 1‐methylimidazol‐2‐yl(pyridin‐2‐yl)methanone and 1‐benzylimidazol‐2‐yl(1‐phenylaldimine)] have been synthesized from hexacarbonylmolybdenum(0) in order to define the coordination characteristics of the bidentate nitrogen‐donor ligands; the complexes exhibit distorted octahedral coordination for molybdenum(0) and cis‐bidentate ligand configurations.     

Arene-promoted lithiation of 1,n-dihaloalkanes (n=2-6): a comparative study

The reaction of 1,n-dichloroalkanes 3a (n=2-6) with an excess of lithium powder and a catalytic amount of 4,4′-di-tert-butylbiphenyl (DTBB; 2.5 mol %) in the presence of different carbonyl compounds [Bu^tCHO, PhCHO, Et₂CO, (CH₂)₄CO, (CH₂)₅CO, (CH₂)₇CO, (−)-menthone], in THF at −78 °C leads, after hydrolysis with water, to the expected 1,(n+2)-diols 4, yields being <25% for n=2, 3 and in the range of 45-79% for n=4-6. When the same protocol is applied to 1,n-bromochloroalkanes 3b and 1,n-dibromoalkanes 3c (n=2-6), diols 4 are obtained in general with lower yields.     

Novel synthesis of 2,4-bis(2-pyridyl)-5-(pyridyl)imidazoles and formation of N-(3-(pyridyl)imidazo[1,5-a]pyridine)picolinamidines: nitrogen-rich ligands

Heating a neat 1:2 mixture of 2-picolylamine and 2-cyanopyridine followed by treatment of the resultant red gummy substance with aqueous KOH resulted in the isolation of 2,4,5-tris(2-pyridyl)imidazole (1a) as the major product and N-(3-(2-pyridyl)imidazo[1,5-a]pyridine)picolinamidine (2a) in small amounts. Similarly, by using 3-picolylamine, 2,4,-bis(2-pyridyl)-5-(3-pyridyl)imidazole (1b) and N-(3-(3-pyridyl)imidazo[1,5-a]pyridine)picolinamidine (2b) were isolated, and by using 4-picolylamine, 2,4,-bis(2-pyridyl)-5-(4-pyridyl)imidazole (1c) and N-(3-(4-pyridyl)imidazo[1,5-a]pyridine)picolinamidine (2c) were isolated. The plausible mechanism of the formation of 1a-c and 2a-c is delineated.     

Reversed-phase high-performance liquid chromatographic/mass spectrometric method for separation of 4-methylimidazole and 2-acetyl-4-(1,2,3,4-tetrahydroxybutyl)imidazole at pg levels

A high-performance liquid chromatographic/mass spectrometric method (HPLC/MS) has been developed to determine both 4-methylimidazole (4MeI) and 2-acetyl-4-(1,2,3,4-tetrahydroxybutyl)imidazole (THI) in one run. Among three sorbents tested, the best peak shape of 4MeI was achieved on a reversed-phase MetaChem Polaris C18-A at pH 9.5. The sensitivity and the range of UV detection at 215 and 290 nm for 4MeI and THI, respectively, were compared to the parameters achieved by the electrospray ionization mass spectrometric (ESI/MS) detection in the presence of 5 mmol l⁻¹ ammonium hydroxide using selected ion-monitoring (SIM) mode. The on-column limits of detection were 0.147 ng of 4MeI and 0.084 ng of THI using UV detection and 1 pg of 4MeI and 3 pg of THI using ESI/MS detection, respectively. The effect of both ammonium ion concentration and energy of fragmentation on 4MeI and THI ionization is discussed. The method could be applied for a fast and sensitive determination of 4MeI and THI in different biological materials as well as in Class III Caramels.     

Ionene-Bound Borohydrides: Efficient, Selective, and Versatile Polymer-Supported Reducing Agents

Summary. Reduction of structurally different carbonyl compounds, such as aldehydes, ketones, α,β-unsaturated enals and enones, acid chlorides, and imines was accomplished efficiently using high capacity ionene based borohydride reagents. Aldehydes and imines were reduced to the corresponding alcohols and amines in excellent yields in methanol at ambient temperature while ketones and acid chlorides were reduced in iso-propanol and THF-MeOH at reflux. Chemoselective reduction of aldehydes over ketones was achieved successfully with these reagents. Complete regioselectivity was also observed in the reduction of α,β-unsaturated aldehydes and ketones.     

[(Ph)2(NMe2)C(OLi)⋅THF]2: Crystal Structure of the Tetrahedral Intermediate Formed in the Reaction of N,N-Dimethylbenzamide and Phenyllithium

Information on the reaction path for the 1,2-eliminiation of LiNMe₂ to form benzophenone is provided by the X-ray crystal structure analysis of the tetrahedral adduct [(Ph)₂(NMe₂)C(OLi)⋅THF]₂ (a portion of the structure is shown schematically), which is prepared from N,N-dimethylbenzamide and phenyllithium. A N1−Li1 interaction, which is not observed, would lead to loss of the anomeric effect (n_N→σ^*_C−O) as well as high conformational strain along the C1−N1 bond.     

Determination Co2+ in vitamin B12 based on enhancement of 2-(4-substituted-phenyl)-4,5-di(2-furyl) imidazole and H2O2 chemiluminescence reaction

In this paper, three kinds of imidazole derivatives, 2-(4-methylphenyl)-4,5-di(2-furyl) imidazole (MDFI), 2-(4-nitrophenyl)-4,5-di(2-furyl) imidazole (NDFI), and 2-(4-tert-butylphenyl)-4,5-di(2-furyl) imidazole (t-BDFI) were synthesized. In an alkaline medium, the chemiluminescence (CL) reaction of imidazole derivatives with H₂O₂ has been investigated. It was also found that MDFI/H₂O₂ and t-BDFI/H₂O₂ systems gave strong CL. When Co²⁺ was added into the two CL systems, the CL intensity was remarkably enhanced. In the optimum conditions, the CL intensity is linearly related to the logarithm of concentration of Co²⁺. The linear ranges are 5 × 10⁻⁹–2.5 × 10⁻⁷ mol/L for MDFI/H₂O₂ system and 5 × 10⁻⁹–2.5 × 10⁻⁷ mol/L for t-BDFI/H₂O₂ system, and the corresponding detection limits are 1.2 × 10⁻⁹ mol/L and 1.1 × 10⁻⁹ mol/L, respectively. The method was applied to the determination of Co²⁺ in vitamin B₁₂ injection. Furthermore, the CL mechanism was also discussed.     

Lateral lithiation in terpenes: synthesis of (+)-ferruginol and (+)-sugiol

This paper describes the use of (−)-sclareol in the synthesis of the tricyclic diterpenes of abietane skeleton, such as (+)-ferruginol and (+)-sugiol, using as key step the lateral lithiation of a dinorditerpene derivative.     

An efficient synthesis of cyanoarenes and cyanoheteroarenes via lithiation followed by electrophilic cyanation

A one-pot procedure for the conversion of mono-substituted arenes and heteroarenes into the ortho-cyano derivatives was achieved through directed lithiation followed by electrophilic cyanation with phenyl cyanate. This reaction method proved to be applicable to halogen-lithium exchanged intermediates, so especially useful for the synthesis of benzonitriles. The scope of the reaction sequence was explored using a number of substrates.     

One-pot synthesis of 2-(dicyanomethylene)-1,2-dihydropyridine derivatives

The synthesis of 2-(dicyanomethylene)-1,2-dihydropyridine derivatives from the reactions of arylmethylidene derivatives of malononitrile dimers with 1,3-dicarbonyl compounds is described.     

2-Substituted imidazoles. 1. Reactions of 1-methyl-2-(2-furyl)imidazole with electrophiles

1-Methyl-2-(2-furyl)imidazole has been synthesized. Electrophilic attack (bromination, nitration, formylation, acylation, and hydroxymethylation) occurs in most cases at the free -position of the furan ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1396–1400, October, 1989.     

An expeditious synthesis of cyanohydrin trimethylsilyl ethers using tetraethylammonium 2-(carbamoyl)benzoate as a bifunctional organocatalyst

Phthalimide and tetraethylammonium hydroxide react via an unusual pathway to afford tetraethylammonium 2-(carbamoyl)benzoate (TEACB) which is of interest as a bifunctional organocatalyst. TEACB (0.5 mol %) was found to catalyze the addition of trimethylsilyl cyanide (TMSCN) to carbonyl compounds under solvent-free conditions at room temperature with very short reaction times. A wide variety of aldehydes and ketones were transformed into the corresponding cyanohydrin trimethylsilyl ethers in high to quantitative yields.     

Azomethine Imines in Four- and Five-Membered Rings: Stable Cyclic Valence Isomers of an α-(Phenyldiazenyl)ketocarbene

The expected Wolff rearrangement of the ketocarbene intermediate 2 , formed upon rhodium(II )-catalyzed elimination of nitrogen from diazoketone 1 , does not occur. Instead, by incorporation of the neighboring diazene group the surprisingly stable, crystalline azomethine imines 3 and 4 are formed as cyclic valence isomers of 2 . Compound 4 , which contains a five-membered ring, is the first representative of a carba-sydnone and can also be obtained by acid-catalyzed isomerization of 3 at 50–70°C.     

Syntheses of 2-(2-arylethyl)imidazoles

Condensation of 2-methylimidazole with arylaldehyde 4 and subsequent reduction of the intermediate 5 with Raney-nickel gave 2-[2-(2,4-dichlorophenyl)ethyl]imidazole 2 . Compound 11 was prepared from compound 10 similarly. Reaction of compound 2 with methylsulfonyl chloride gave 1-methylsulfonyl-2-[2-(2,4-dichlorophenyl)ethyl]imidazole ( 7a ) in moderate yield. Nitration of compound 11 (Ar = 3-pyridyl) gave the desired nitro compounds 14 and 15 .