Novel imidazole ring formation from .alpha. olefins, carbon monoxide, and ammonia

Iwashita, Yuji; Sakuraba, Mitsuru

doi:10.1021/jo00824a017

Cited by 20 publications

(4 citation statements)

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“…2,4,5-Triethyl-1H-imidazole (2k). 37 This compound was synthesized according to the general procedure; substrate 1l (114.0 mg, 1.0 mmol), ammonium formate (315 mg, 5.0 mmol), and Ru4 (47.5 wt % Ru, 2.2 mg, 1.0 mol %) in anhydrous DMF (3.0 mL) were stirred at 85 °C for 16 h. The title compound was isolated after flash chromatography as a viscous oil (90 mg, 89% yield). 1 H NMR (300 MHz, CDCl 3 ): δ 1.16 (t, J = 7.6 Hz, 6 H), 1.24 (t, J = 7.6 Hz, 3 H), 2.50 (q, J = 7.7 Hz, 4 H), 2.67 (q, J = 7.7 Hz, 2 H), 5.5−6.0 (bs, 1H).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Phosphine Supported Ruthenium Nanoparticle Catalyzed Synthesis of Substituted Pyrazines and Imidazoles from α-Diketones

Prasad

Leeuwen

2017

J. Org. Chem.

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A new methodology has been developed for the synthesis of highly substituted nitrogen heterocycles such as pyrazines and imidazoles starting from α-diketones using phosphine supported ruthenium nanoparticles (RuNPs) as catalysts. Ruthenium nanoparticles Ru1-Ru4 supported with different phosphines such as dbdocphos, dppp, DPEphos, and Xantphos are screened, of which Ru1 and Ru4 are found to be the most active. Interestingly, aryl-substituted and alkyl-substituted α-diketones produced different products: namely, pyrazine and imidazoles, respectively. This reaction methodology has been applied to the synthesis of a key intermediate (2m) of the marine cytotoxic natural product Dragmacidin B and an estrogen receptor (2l). This work represents the first examples of pyrazines prepared by RuNPs.

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Section: ■ Experimental Sectionmentioning

confidence: 99%

Phosphine Supported Ruthenium Nanoparticle Catalyzed Synthesis of Substituted Pyrazines and Imidazoles from α-Diketones

Prasad

Leeuwen

2017

J. Org. Chem.

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“…Surprisingly, there are limited synthetic routes towards 2,4,5-trisubstituted imidazoles commencing from alkenes and one of the earliest reports involves the use of a rhodium oxide catalyst and ammonia in a methanol-water mixture in the presence of carbon monoxide (Scheme 1b). 15 The challenges associated with this approach include the use of an expensive rhodium catalyst, employment of toxic carbon 186…”

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confidence: 99%

Acid, Metal and Peroxide-Free Synthesis of 2,4,5-Trisubstituted Imidazoles Commencing from Internal Alkenes Using an Iodine/DMSO System

Jeena¹,

Majola²

2023

HETEROCYCLES

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An efficient acid, metal and peroxide-free synthesis of 2,4,5trisubstituted imidazoles commencing from internal alkenes and aldehydes using an inexpensive and eco-friendly iodine/DMSO system has been reported. This simple methodology affords a plethora of 2,4,5-trisubstituted imidazoles in moderate to good yields under mild reaction conditions. Based on preliminary control studies, a reasonable mechanism to the target imidazole is proposed.Oxidations play a vital role in academia and industry as it assists in the creation of new, complex molecules or the modification of existing ones. 1 Given the importance of this transformation, the demand for novel, environmentally benign, and cost-effective oxidation methods have steadily increased. 2 Within this context, the oxidation of alkenes, in particular, continues to be of importance as it is used to prepare epoxides, 3 carbonyls, 4 and 1,2-diols. 5 Additionally, the conversion of internal alkenes to α-diketones is of interest to organic chemists as it allows for the generation of synthetically useful compounds such as quinoxalines and spirocycles. 6 Hence, a multitude of synthetic routes have been devised for the conversion of internal alkenes to α-diketones and selected examples include the use of potassium permanganate in acetic anhydride 7 and ruthenium-catalyzed hydrogen abstraction. 8 2,4,5-Trisubstituted imidazoles are important heterocyclic compounds as they display interesting biological 9,10 and synthetic applications. 11 The traditional route towards these fascinating molecules involves the multicomponent reaction of a α-diketone, aldehyde and ammonium acetate in the presence of a metal or acid catalyst (Scheme 1a) such as acetic acid, 12 ytterbium triflate, 13 and (NH4)6Mo7O24•4H2O, 14 to name but a few. Surprisingly, there are limited synthetic routes towards 2,4,5-trisubstituted imidazoles commencing from alkenes and one of the earliest reports involves the use of a rhodium oxide catalyst and ammonia in a methanol-water mixture in the presence of carbon monoxide (Scheme 1b). 15 The challenges associated with this approach include the use of an expensive rhodium catalyst, employment of toxic carbon 186

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“…In 1971, Iwashita and Sakuraba reported the preparation of 2,4,5-trisubstituted imidazoles from alkenes, carbon monoxide and ammonia in the presence of rhodium oxide to give 2,4,5-trialkyl imidazole as the major product and an amide as a minor product (Scheme 26). 172 The imidazoles synthesized by this method were obtained in fair to moderate yields (40 -60%). However, this system was not applicable to internal alkenes as cyclohexene reaction only gave the amide and amines as products.…”

Section: Use Of Rhodium Oxide Catalystmentioning

confidence: 95%

“…The preparation of 2,4,5-trisubstituted imidazoles commencing from alkenes has been explored using harsh reaction conditions, expensive catalysts, toxic reagents, and laborious work up. [172][173][174] Herein, we propose the synthesis of these compounds commencing from alkenes using a suitable system that is simple, metal-and acid-free, environmentally friendly and uses cheap reagents under mild reaction conditions. This study involves the oxidation of alkenes into 1,2-diketones which would then be coupled with aldehydes and ammonium acetate to furnish the desired imidazoles (Scheme…”

Section: Proposed Synthesismentioning

confidence: 99%

One-pot, multicomponent oxidative synthesis of 2,4,5-trisubstituted imidazoles from internal alkenes using an I2/DMSO system.

Majola

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Imidazoles are vital heterocyclic compounds usually incorporated in natural products such as biotin, vitamin B12, histamine, and histidine. 2,4,5-trisubstituted imidazoles, in particular, possess versatile biological and pharmaceutical activities such as antidiabetic, antimalarial, and analgesic properties. A traditional procedure for the synthesis of these elegant compounds involves the cyclocondensation reaction between a 1,2-diketone, an aldehyde, and ammonia in the presence of an acid or metal catalyst. However, this methodology suffers from various shortcomings such as the use of acid or metal catalysts, tedious work-up procedures, use of toxic reagents, and substrate scope limitations. Hence, the development of new methods to synthesize 2,4,5-trisubstituted imidazoles is of vital importance. This study describes the preparation of 2,4,5-trisubstituted imidazoles from alkenes using an environmentally benign iodine/DMSO system. This novel methodology was applied to a broad substrate scope such as substituted benzaldehydes, heterocyclic aldehydes, bulkier aldehydes, and substituted stilbenes, and afforded the target compounds in moderate to high yields under mild reaction conditions. Preliminary mechanistic studies revealed that 1,2-diketone is a key intermediate and that the mechanism is not radical-mediated. It also revealed that the oxygen source is DMSO and that the coupling step is catalyzed by iodine coordination and hydrogen bonding from the solvent. Based on the results obtained from the preliminary mechanistic investigations, a reasonable mechanism is proposed.

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Novel imidazole ring formation from .alpha. olefins, carbon monoxide, and ammonia

Abstract: 2-Amino-4-hydroxy-6-phenylpteridine.-2,4,5-Triamino-6hydroxypyrimidine sulfate (2.0 g, 8.4 mmol) was suspended in 30 ml of H20, and BaCl2-2H20 (2.0 g, 8.4 mmol) was added.

Cited by 20 publications

References 0 publications

Phosphine Supported Ruthenium Nanoparticle Catalyzed Synthesis of Substituted Pyrazines and Imidazoles from α-Diketones

Phosphine Supported Ruthenium Nanoparticle Catalyzed Synthesis of Substituted Pyrazines and Imidazoles from α-Diketones

Acid, Metal and Peroxide-Free Synthesis of 2,4,5-Trisubstituted Imidazoles Commencing from Internal Alkenes Using an Iodine/DMSO System

One-pot, multicomponent oxidative synthesis of 2,4,5-trisubstituted imidazoles from internal alkenes using an I2/DMSO system.

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