Reaction of 2-(4'-Thiazolyl)benzimidazole (thiabendazole) with alkyl halides

1971 ◽  
Vol 24 (9) ◽  
pp. 1873 ◽  
Author(s):  
JA Maynard ◽  
ID Rae ◽  
D Rash ◽  
JM Swan
Keyword(s):  
Alkyl Halide ◽  
Sodium Hydride ◽  
Alkyl Halides ◽  
Benzimidazole Ring ◽  
Ring Systems ◽  
Quaternary Salts ◽  
Spectroscopic Examination

2-(4?-Thiazolyl)benzimidazole (thiabendazole) is alkylated at a benzimidazole nitrogen by reaction with sodium hydride and an alkyl halide. With 1,3-dibromo-propane and 1,2-dibromoethane, the thiazole nitrogen is also alkylated to give quaternary salts containing the 6,7- dihydro-5H-thiazolo[3?,4?:1.2][1,4]diazepino-[8,9-a]benzimidazole and 5,6-dihydrothiazolo[3?,4?:1,2]pyrazino[7,8-a]benzimidazole ring systems respectively. The structures proposed for these tetracyclic products are supported by spectroscopic examination of the products formed by alkali fission of their thiazole rings.

Efficient dehydrative alkylation of thiols with alcohols catalyzed by alkyl halides

2017 ◽  
Vol 15 (45) ◽  
pp. 9638-9642 ◽  
Author(s):  
Yaqi Yang ◽  
Zihang Ye ◽  
Xu Zhang ◽  
Yipeng Zhou ◽  
Xiantao Ma ◽  
...  
Keyword(s):  
Transition Metal ◽  
Alkyl Halide ◽  
Alkyl Halides ◽  
Alkylation Reaction

Alcohols can be efficiently converted into thioethers by a transition metal- and base-free alkyl halide-catalyzed S-alkylation reaction with thiols or disulfides.

Binding of alkyl halides in water-soluble cavitands with urea rims

2018 ◽  
Vol 42 (12) ◽  
pp. 9945-9948 ◽  
Author(s):  
Yang Yu ◽  
Yong-Sheng Li ◽  
Julius Rebek
Keyword(s):  
Alkyl Halide ◽  
Alkyl Halides ◽  
Water Soluble

Alkyl halide guests in cavitands move rapidly and maintain halide to contact with the aryl surfaces of the host.

scholarly journals Recent advances in copper-catalyzed asymmetric coupling reactions

2015 ◽  
Vol 11 ◽  
pp. 2600-2615 ◽  
Author(s):  
Fengtao Zhou ◽  
Qian Cai
Keyword(s):  
Recent Progress ◽  
Alkyl Halides ◽  
Coupling Reactions ◽  
Ring Systems ◽  
The Past ◽  
Recent Advances ◽  
Asymmetric Coupling ◽  
Significant Attention

Copper-catalyzed (or -mediated) asymmetric coupling reactions have received significant attention over the past few years. Especially the coupling reactions of aryl or alkyl halides with nucleophiles became a very powerful tool for the formation of C–C, C–N, C–O and other carbon–heteroatom bonds as well as for the construction of heteroatom-containing ring systems. This review summarizes the recent progress in copper-catalyzed asymmetric coupling reactions for the formation of C–C and carbon–heteroatom bonds.

scholarly journals Hetarylazopyrazolone Dyes Based on Benzothiazole and Benzimidazole Ring Systems: Synthesis, Spectroscopic Investigation, and Computational Study

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Ebru Aktan ◽  
Tahsin Uyar
Keyword(s):  
Density Functional Theory ◽  
Density Functional ◽  
Computational Study ◽  
Benzimidazole Ring ◽  
Acid Base ◽  
Functional Theory ◽  
Ring Systems ◽  
Td Dft ◽  
Elemental Analyses ◽  
Experimental Values

In this study, the synthesized coupling component 1-(2-benzothiazolyl)-3-methylpyrazol-5-one reacted with diazotised heterocyclic amines to afford six novel hetarylazopyrazolone dyes. These azo dyes based on benzothiazole and benzimidazole ring systems were characterized by spectral methods and elemental analyses. The solvatochromic behaviors of these dyes in various solvents were evaluated. The ground state geometries of the dyes were optimized using density functional theory (DFT). Solvent, acid-base, and substituent influences on the wavelength of the maximum absorption were examined in detail. Time-dependent density functional theory (TD-DFT) calculations were performed to obtain the absorption spectra of the dyes in various solvents and the results compared with experimental values. Besides, frontier molecular orbitals (FMO) analysis for the dyes is also described from the computational process.

scholarly journals Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

2021 ◽  
Vol 17 ◽  
pp. 1939-1951
Author(s):  
Ryan M Alam ◽  
John J Keating
Keyword(s):  
Alkyl Halide ◽  
Sodium Hydride ◽  
Product Yield ◽  
Efficient Synthesis ◽  
Initial Screening ◽  
Electronic Effects ◽  
Therapeutic Drugs ◽  
Alkylating Reagents ◽  
High Degree ◽  
The Impact

The indazole scaffold represents a promising pharmacophore, commonly incorporated in a variety of therapeutic drugs. Although indazole-containing drugs are frequently marketed as the corresponding N-alkyl 1H- or 2H-indazole derivative, the efficient synthesis and isolation of the desired N-1 or N-2 alkylindazole regioisomer can often be challenging and adversely affect product yield. Thus, as part of a broader study focusing on the synthesis of bioactive indazole derivatives, we aimed to develop a regioselective protocol for the synthesis of N-1 alkylindazoles. Initial screening of various conditions revealed that the combination of sodium hydride (NaH) in tetrahydrofuran (THF) (in the presence of an alkyl bromide), represented a promising system for N-1 selective indazole alkylation. For example, among fourteen C-3 substituted indazoles examined, we observed > 99% N-1 regioselectivity for 3-carboxymethyl, 3-tert-butyl, 3-COMe, and 3-carboxamide indazoles. Further extension of this optimized (NaH in THF) protocol to various C-3, -4, -5, -6, and -7 substituted indazoles has highlighted the impact of steric and electronic effects on N-1/N-2 regioisomeric distribution. For example, employing C-7 NO2 or CO2Me substituted indazoles conferred excellent N-2 regioselectivity (≥ 96%). Importantly, we show that this optimized N-alkylation procedure tolerates a wide structural variety of alkylating reagents, including primary alkyl halide and secondary alkyl tosylate electrophiles, while maintaining a high degree of N-1 regioselectivity.

scholarly journals Green Chemistry: Comparison of Ionic Liquid vs Conventional Solvent for Indole Alkylation

2016 ◽  
Vol 13 (4) ◽  
Author(s):  
Jonathan Redrico ◽  
John Krstenansky
Keyword(s):  
Ionic Liquid ◽  
Green Chemistry ◽  
Conventional Method ◽  
Potassium Hydroxide ◽  
Alkyl Halide ◽  
Sodium Hydride ◽  
Synthetic Methods ◽  
Sustainable Chemistry ◽  
Reaction Yield ◽  
Green Method

A comparison of the effectiveness of two synthetic methods was done for a green chemistry method using an ionic liquid-based solvent relative to a conventional method using organic solvents for the N-alkylation of indole. The green method used potassium hydroxide in the ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate, followed by addition of the alkyl halide. The conventional method used sodium hydride in dimethylformamide. Possible advantages of the green method would be the use of a non-volatile solvent, the possibility of recycling the solvent, and the use of a less reactive base. However, its reaction yield was lower than for the conventional method, the reagent expense was higher, and recycling and reuse of the ionic solvent require considerable amounts of conventional solvent to clean it up sufficiently for reuse. On a laboratory scale, the ionic liquid method yielded neither a “green” nor an efficiency advantage. It is possible that with optimization on an industrial scale involving solvent reclamation that the green method could realize its promise. KEYWORDS: Green Chemistry; Sustainable Chemistry; Ionic Liquids; N-alkylation; Indole; Solvent Recycling; Organic Chemistry; 1-Butyl-3-methylimidazolium Tetrafluoroborate; Synthesis

scholarly journals Electrochemically Driven Cross-Electrophile Coupling of Alkyl Halides

2021 ◽  
Author(s):  
Song Lin ◽  
Wen Zhang ◽  
Lingxiang Lu ◽  
Wendy Zhang ◽  
Jose Mondragon ◽  
...  
Keyword(s):  
High Selectivity ◽  
Alkyl Halide ◽  
Cross Coupling ◽  
Alkyl Halides ◽  
Critical Problem ◽  
Metal Free ◽  
Drug Candidates ◽  
Synthetic Accessibility ◽  
Alkyl Electrophiles ◽  
Direct Cross

Recent research in medicinal chemistry suggests a correlation between an increase in the fraction of sp3 carbons in drug candidates with their improved success rate in clinical trials. As such, the development of robust and selective methods for the construction of C(sp3)-C(sp3) bonds remains a critical problem in modern organic chemistry. Owing to the broad availability and synthetic accessibility of alkyl halides, their direct cross coupling—commonly known as cross-electrophile coupling (XEC)—provides a promising route toward this objective. However, achieving high selectivity in C(sp3)-C(sp3) XEC remains a largely unmet challenge. Herein, we employ electrochemistry to achieve the differential activation of alkyl halides by exploiting their disparate electronic and steric properties. Specifically, the selective cathodic reduction of a more substituted alkyl halide gives rise to a carbanion, which undergoes preferential coupling with a less substituted alkyl halide via bimolecular nucleophilic substitution (SN2) to forge a new C–C bond. This transition-metal free protocol enables the efficient XEC of a variety of functionalized and unactivated alkyl electrophiles and exhibits substantially improved chemoselectivity versus existing methodologies.

The N-Alkylation of Sulfoximines

1986 ◽  
Vol 39 (10) ◽  
pp. 1655 ◽  
Author(s):  
B Raguse ◽  
DD Ridley
Keyword(s):  
Sodium Hydride ◽  
Alkyl Halides ◽  
Optimal Temperature ◽  
Temperature Conditions

Reactions of sulfoximines with sodium hydride in dimethylformamide, then with a variety of alkyl halides afford N- alkylsulfoximines. Generally yields are in excess of 60% under optimal temperature conditions (60�).

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